RARE DISEASE
Chikungunya
Chikungunya
Chikungunya
Drug discovery
2,007
papers
On emerging therapies
Overview
Chikungunya is a mosquito-borne viral illness caused by the Alphavirus CHIKV, transmitted by Aedes aegypti and A. albopictus mosquitoes [1][5][13]. It presents with abrupt fever, debilitating polyarthralgia, myalgia, rash, and headache [1][7][14]. Chronic joint pain persists in 30-50% of cases for months to years [7][15]. Diagnosis relies on RT-PCR (acute phase) or IgM serology (after 5-7 days) [5][13]. Treatment is supportive with acetaminophen, hydration, and rest [1][5][19].
Population
Endemic in 104+ countries across Africa, Asia, the Americas (excluding Canada, Chile, Uruguay, and continental US), and parts of Europe [3][6][10]
2023 outbreaks occurred in Paraguay (138,730 cases), Argentina, and Uruguay (first local transmissions) [2][6]
High-risk groups: Neonates, adults >65 years, and those with hypertension/diabetes [7][11][13]
Burden
Global annual incidence: ~33.7M infections (16.9M symptomatic), with 3.4M chronic cases and 22,600 deaths [3][7]
43.8% of patients report persistent symptoms at 3 months; 17% require hospitalization [7][11][16]
2023 Americas outbreak: >214,000 cases by April, straining healthcare systems in Paraguay/Bolivia [2][6]
Therapies
First-line: Acetaminophen for fever/pain (avoid NSAIDs until dengue excluded) [1][5][19]
Chronic management: NSAIDs, low-dose corticosteroids, or disease-modifying antirheumatic drugs [4][15][18]
IXCHIQ vaccine (live-attenuated) approved for high-risk travelers/lab workers in 2023; not yet deployed in endemic regions [9][13]
Categories: rare infectious diseases, rare neurological diseases
Research Papers
2,007 drug discovery papers about Chikungunya. Recent publications:
2,007 drug discovery papers about Chikungunya. Recent publications:
categories:
Small molecules
proteins
2026-09-06 | Scorpion Peptides in Antiviral Drug Discovery: An In-depth Review.
Despite remarkable progress in the fields of vaccinology and antiviral therapy, viral infections persist as a leading cause of morbidity and mortality worldwide. Therefore, it is crucial to identify new and effective antiviral drug candidates. Scorpion venoms are viewed as a rich source of structurally diverse and biologically active peptides, which may present opportunities for diagnostic, preventive, and therapeutic applications. This review intends to provide a contemporary and detailed analysis of scorpion-derived peptides, with a particular focus on their structural diversity, cytotoxic effects, antiviral properties, and mechanisms of action. Additionally, this paper highlights several potential fruitful areas for future studies. Current evidence indicates that scorpion-derived peptides are effective against a wide array of medically important viral pathogens such as chikungunya virus, dengue virus, enterovirus 71, hepatitis B virus (HBV), herpes simplex virus 1, human immunodeficiency virus 1, influenza A virus (IAV), severe acute respiratory syndrome coronavirus-2, and Zika virus. Nevertheless, the majority of these findings have been obtained from in vitro studies, whereas evidence from animal models remains limited and clinical evaluation in humans is currently unavailable. Available studies suggest that these peptides may act through diverse mechanisms of action, including direct virucidal activity, inhibition of viral entry, immune system modulation, reduction of virus-induced cytopathic effects, and suppression of viral gene expression. Emerging evidence also demonstrates the efficacy of certain scorpion-derived peptides in animal models of HBV, IAV, and Newcastle disease virus infection. Overall, such peptides appear to inaugurate new avenues for the treatment of viral infections.
2026-08-20 | Lachesin is a mosquito receptor for multiple arthritogenic alphaviruses.
Arthritogenic alphaviruses cause acute febrile illnesses associated with rash and arthritis when they are transmitted to humans through the bite of infected mosquitoes. Among these, chikungunya virus (CHIKV), transmitted primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, causes explosive outbreaks involving hundreds of thousands to millions of cases, with recent re-emergence in several global regions. While several cellular receptors that mediate alphavirus entry into mammalian cells have been identified, their mosquito counterparts remained unknown, largely due to a lack of functional genomics tools for these invertebrate species. Here, we established a CRISPR-based genetic screening platform in Aedes albopictus cells and used it to identify Lachesin, a conserved invertebrate cell adhesion molecule, as a receptor for CHIKV and multiple related alphaviruses including Semliki Forest virus (SFV), o'nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). Lachesin depletion using RNA interference, anti-Lachesin antibody treatment, and soluble forms of Lachesin blocked CHIKV and SFV E2-E1 glycoprotein-mediated infection of mosquito cells. We show that alphavirus E2-E1 glycoproteins bind the first immunoglobulin domain of Lachesin, facilitating attachment and internalization of virus-like particles. Orthologs from divergent mosquito genera, but not from arachnids or other arthropods, also serve as alphavirus receptors, suggesting that cellular receptor binding is not the main obstacle to arthritogenic alphavirus vector host expansion. Our findings enhance understanding of the mechanisms of alphavirus emergence and vector competence and could aid in the development of broadly active, entry-targeted therapeutics against multiple alphaviruses that threaten public health.
2026-08-20 | Molecular basis for chikungunya virus recognition of a mosquito-specific receptor.
Alphaviruses are arthropod-borne viruses that recognize cellular receptors in both vertebrate hosts and mosquito vectors to complete their transmission cycle, yet how they maintain recognition of receptors across evolutionarily divergent host species remains unresolved. Among alphaviruses, chikungunya virus (CHIKV), which is primarily vectored in urban settings by Aedes species mosquitoes, is the most widespread, and causes explosive outbreaks that can involve hundreds of thousands to millions of cases annually. The cell adhesion protein Lachesin is a mosquito-specific cellular receptor for CHIKV and multiple other arthritogenic alphaviruses. The envelope E2-E1 glycoproteins of these alphaviruses broadly recognize Lachesin orthologs from diverse mosquito species, but not other insects or arachnids. Lachesin genetic manipulation to prevent mosquito virus infection without interfering with endogenous receptor function could have a major impact for CHIKV control. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of alphaviruses bound to Aedes albopictus Lachesin. Comparative analysis of Lachesin-bound CHIKV, Semliki Forest virus (SFV), and Middelburg virus (MIDV) revealed that these three genetically divergent viruses use a similar surface to recognize Lachesin domain 1, but with reorganized E2-E1 glycoprotein contact residues. We show that a soluble Ae. albopictus Lachesin receptor decoy protein blocks the E2-E1-mediated entry of CHIKV and other arthritogenic alphaviruses into mammalian cells with greater breadth than a vertebrate receptor MXRA8 decoy and protects against lethal SFV challenge and CHIKV pathogenesis in murine models. Additionally, we identified a naturally occurring single residue Lachesin polymorphism that is found in some Anopheles (malaria vector) mosquitoes, and fully ablates CHIKV E2-E1 recognition, informing strategies for mosquito-targeted genetic interventions that could prevent mosquito vector infection and virus transmission. These findings define distinct determinants of receptor binding in mosquitoes and humans for arthritogenic alphaviruses, with implications for countermeasure development and outbreak preparedness.
2026-07-28 | Low-Dose Interleukin-2 Enhances Activated Suppressor Regulatory T Cells and CTLA-4 and HLA-DR Expression in Chronic Chikungunya Arthritis.
Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood mononuclear cells from adults with laboratory-confirmed chronic chikungunya arthritis in Atlántico, Colombia. Cells were treated ex vivo with recombinant IL-2 or an IL-2/anti-IL-2 monoclonal antibody complex in the presence of CD2/CD3/CD28 stimulation beads, followed by flow cytometric assessment of effector T cells and Tregs. Low-dose IL-2 treatments ex vivo did not increase total Treg frequency but selectively increased activated suppressor Tregs while decreasing activated T effector cells, enhancing Treg CTLA-4 and HLA-DR expression, and reducing Ki67 expression in effector T cells. IL-2 complex treatment decreased cytokine-secreting Tregs, and IL-10 and TGF-β were not associated with IL-2 treatment status or with Teff/Treg balance, suggesting limited utility as pharmacodynamic biomarkers of low-dose IL-2 treatments. These findings support the use of activated suppressor Tregs, Treg CTLA-4, and HLA-DR expression as candidate biologic endpoints for evaluation in future trials of low-dose IL-2 in chikungunya arthritis.
2026-07-21 | Ewing sarcoma breakpoint region 1 (EWSR1) protein binds to nonstructural protein 2 and non-coding regions of chikungunya virus genome to inhibit virus replication.
Chikungunya virus (CHIKV) is an alphavirus with a single-stranded RNA genome. Conserved sequence elements within the 5' and 3' non-coding regions (NCRs) of the CHIKV genome interact with host proteins to regulate viral RNA replication. Electrophoretic mobility shift assays (EMSAs) and mass spectrometry identified several host RNA-binding proteins that associate with these conserved NCR elements, among which EWSR1 uniquely bound the 3' ends of both the plus-sense genomic RNA and the minus-sense replication intermediate RNA. EMSA and biolayer interferometry (BLI) demonstrated that EWSR1 binds strongly to two RNA elements: a 48-nucleotide region in the plus-strand 3'-NCR (3NCR48) and a 50-nucleotide region at the 3'-end of the minus-strand replication intermediate (5NCR-RC50), which is complementary to the genome's 5'-NCR and its adjacent sequence. RNA immunoprecipitation from CHIKV-infected cells confirmed that EWSR1 binds CHIKV RNA in vivo. Functional analyses revealed that CHIKV infection downregulates EWSR1 expression and causes its accumulation in the cytoplasm. Knockdown or knockout (KO) of EWSR1 expression increased CHIKV genomic RNA levels and viral titers, whereas its overexpression suppressed both. EWSR1 reduced the synthesis of both plus- and minus-sense CHIKV RNAs in infected cells. Additionally, EWSR1 was found to bind to CHIKV nsP2 and inhibit its helicase activity, which is critical for viral genome replication. The antiviral activity of EWSR1 extended to Ross River virus but not to Sindbis virus, consistent with conservation of the 48-nucleotide sequence in their respective 3'-NCRs. Together, these findings identify EWSR1 as a novel host restriction factor that limits CHIKV replication through specific interactions with viral RNA and the nsP2 protein.IMPORTANCEChikungunya virus (CHIKV) poses a significant medical challenge, necessitating the development of novel antiviral strategies. This study demonstrates that the host protein EWSR1 plays a key role in controlling CHIKV replication. By binding to specific regions of viral RNA and interacting with nsP2, a critical viral enzyme, EWSR1 inhibits viral RNA synthesis and reduces viral titers. In the absence of EWSR1, CHIKV replicates more efficiently, underscoring its antiviral function. These findings establish EWSR1 as an important host restriction factor that limits CHIKV replication. Understanding this interaction enhances our knowledge of host-virus dynamics and may guide the design of new antiviral approaches against CHIKV and related alphaviruses.
small molecules
2026-09-30 | Neuropilin-1 functions as a proviral and immunoregulatory host factor during Chikungunya virus infection.
Neuropilin-1 (NRP1) is a transmembrane glycoprotein involved in angiogenesis, neurodevelopment, inflammation, cancer driven immune suppression, and immune homeostasis. However, its contribution to virus-induced immune responses is not explored. Chikungunya virus (CHIKV) is a re-emerging arthritogenic alphavirus that causes severe arthralgia, and myalgia, accompanied by heightened inflammatory cytokine responses. The host factors that drive these inflammatory responses, however, remain poorly defined. Here, in this current study, the role of NRP1 in CHIKV infection was investigated using in vitro , and in vivo model systems. Using genetic manipulation, pharmacological, and antibody blockade-mediated approaches in murine and human cellular infection models, it was demonstrated that NRP1 promotes CHIKV infection while restraining the production of proinflammatory cytokines. Furthermore, NRP1 inhibition selectively increased JNK phosphorylation. Hence, inhibiting JNK reduced the elevated cytokine production caused by NRP1 blockade. Moreover, NRP1 interacted with CHIKV-E1 and is involved in multiple phases of CHIKV infection. In addition, it was demonstrated that NRP1 inhibition using EG00229 trifluoroacetate can reduce viral infection in several CHIKV-susceptible cells, human peripheral blood macrophages, and in the in vivo mice model of infection. Together, these findings indicate that NRP1 is an important host factor and a probable therapeutic target during CHIKV infection. Chikungunya virus (CHIKV) causes acute febrile illness that can progress to debilitating chronic musculoskeletal and occasional neurological complications. The absence of a globally available effective vaccine and the lack of specific antivirals underscore CHIKV as a major burden, especially in endemic tropical regions. There is a growing need to understand host factors that shape CHIKV-driven immune response. The importance of our study lies in understanding the immunoregulatory role of the host receptor Neuropilin-1 (NRP1) during CHIKV infection. We identify NRP1 as a novel host factor of CHIKV infection that also acts as a rheostat to restrict the inflammatory viral immune response. Moreover, we report anti-viral potential of the NRP1 antagonist EG00229 trifluoroacetate in multiple cell lines, primary cells, and mice model. Our findings indicate NRP1 as a probable therapeutic target in CHIKV pathogenesis.
2026-09-26 | Synthesis and Broad-Spectrum Antiviral Evaluation of Novel 1,2,3-Triazole-Quinoline Derivatives Targeting SARS-CoV-2, Influenza, DENV-2, and CHIKV.
The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole-quinoline derivatives (compounds 4a-4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a-4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens.
2026-09-25 | Backs under pressure: measuring and estimating lumbar spinal loads.
This issue of the Biomedical Journal examines lumbar spinal loading and current approaches to its assessment using invasive measurements, biomechanical modeling, imaging, wearable technologies, and AI-assisted methods. Other contributions address coumarin derivatives as modulators of autophagy and PI3K/mTOR signaling in cancer and apply multi-omics approaches to uric acid metabolism and cardiometabolic disease. Further studies investigate molecular mechanisms linking mechanical irritation to oral squamous cell carcinoma progression, predictors of HBsAg seroclearance after antiviral treatment withdrawal, and age-dependent effects of exercise and losartan. Additional contributions explore PD-L1 signaling in allergic asthma, the antiviral activity of BPR2-D2 against chikungunya virus replication, and differences in objective tear function between patients with and without mental disorders.
2026-09-15 | Solanaceae-Derived Spirostane Saponins Inhibit Dengue Virus Replication and Viral Protein Expression and Exhibit Activity Against Multiple Arboviruses.
Mosquito-borne arboviruses, including dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV), represent a growing global health burden, yet no specific antiviral therapies are currently available for most of these infections. This unmet need highlights the importance of identifying novel antiviral compounds from biologically relevant sources such as plant-derived natural products. In this study, a bioactivity-guided approach was applied to methanolic extracts from eight Solanaceae species to identify compounds with antiviral activity against DENV-2 in Vero cells. Five extracts significantly reduced viral infectivity, with Solanum ovalifolium and Cestrum sp. achieving complete inhibition at non-cytotoxic concentrations. Subsequent fractionation and purification led to the isolation of four spirostane-type steroidal saponins, structurally characterized by UPLC-DAD-MS and 1D/2D NMR spectroscopy. Functional assays demonstrated that these compounds inhibit DENV replication, as evidenced by marked reductions in viral RNA levels, NS1 and NS3 protein expression, and infectious viral titers. Stage-specific analyses revealed that their antiviral activity is primarily associated with intracellular phases of the viral life cycle, consistent with inhibition of viral replication and/or protein processing. Molecular docking analyses supported these findings by predicting favorable interactions with key viral enzymes, particularly NS5 RNA-dependent RNA polymerase and NS3 helicase/protease. Importantly, the isolated compounds retained antiviral activity against ZIKV and CHIKV, indicating cross-arboviral efficacy. Together, these findings identify spirostane saponins as promising antiviral scaffolds and support their further development as broad-spectrum antiviral agents.
2026-09-14 | Assessing Chikungunya Virus Protease Activity and Pharmacological Inhibition Using the acc-CHIK15-dnp Fluorogenic Peptide Substrate.
Chikungunya virus, a mosquito-borne alphavirus, poses a significant global health threat due to its rapid spread and lack of approved antiviral therapies. The viral nonstructural protein 2 protease (nsP2p) plays a critical role in processing the viral polyprotein to produce key viral enzymes, making it an attractive target for drug development. In this study, we describe the expression and purification of recombinant CHIKV nsP2 protease and establish a robust fluorogenic assay to measure its enzymatic activity using the acc-CHIK15-dnp peptide substrate. The assay enables real-time monitoring of proteolytic cleavage and provides a platform for evaluating small-molecule inhibitors. We present optimized conditions for protein expression in E. coli, affinity purification, and tag removal, achieving high-purity nsP2 protease suitable for biochemical characterization. Using this system, we also provide a robust protocol for determining IC₅₀ values for candidate inhibitors. This work provides a reproducible methodology for high-throughput screening of CHIKV protease inhibitors, facilitating the discovery of potential antiviral compounds against chikungunya virus.
vaccines
2026-09-16 | Development of a potential vaccine against dengue and chikungunya virus co-infection using immunoinformatics and structural evaluation.
Dengue virus (DENV) and chikungunya virus (CHIKV) co-infection poses a growing challenge in regions where both arboviruses co-circulate, highlighting the need for integrated vaccine strategies. Here, we designed a multi-epitope subunit vaccine candidate targeting conserved regions of the DENV NS1 protein and the CHIKV NSP1 protein using an immunoinformatics-based approach. Conserved CTL, HTL, and B-cell epitopes were selected on the basis of antigenicity, safety-related screening, and population coverage, then assembled with immunologically appropriate linkers and an N-terminal human β-defensin-2 adjuvant. The construct displayed favourable physicochemical features and acceptable structural quality after three-dimensional modeling and validation. Docking analysis indicated stable interaction with human TLR4, which was further examined by normal-mode analysis and 100-ns all-atom molecular dynamics simulations performed in AMBER v24 with the ff19SB force field. Trajectory analyses supported conformational stability of the vaccine-TLR4 complex, and MM/GBSA calculations suggested favourable binding energetics. Codon optimization supported expression feasibility in the E. coli pET-28a(+) system. In silico immune simulation further predicted induction of both humoral and cellular immune responses, with increased antibody production and immune-memory development. These results support the proposed construct as a rational candidate for further experimental evaluation toward a vaccine strategy against DENV-CHIKV co-infection.
2026-09-10 | Targeting conserved interaction surfaces of alphavirus nsP4 supports the rational design of live-attenuated vaccine candidates.
Alphaviruses are emerging arboviruses that pose a growing threat to global public health; however, effective interventions remain limited. Recent structural studies of the chikungunya virus (CHIKV) replicase core revealed that the viral RNA-dependent RNA polymerase nsP4 interacts with both nsP1 and nsP2 and is predicted to engage viral RNA. The conservation and multifunctionality of nsP4 make it a challenging but promising target for rational attenuation. Here, we evaluated 58 structure-guided mutations in nsP4 predicted to disrupt interactions with nsP1, nsP2, or viral RNA using a trans-replicase system. Sixteen selected mutations were further analyzed in a CHIKV-o'nyong-nyong virus chimera and Semliki Forest virus (SFV). Most mutants were viable but showed varying degrees of attenuation in mammalian and mosquito cells. Viruses carrying mutations in predicted RNA-interaction sites frequently acquired pseudoreversions and/or second-site compensatory changes, whereas those harboring mutations affecting nsP1 or nsP2 interfaces were more genetically stable. Three substitutions representing defects in nsP1 interaction (F164A), predicted RNA interaction (K174S), and nsP2 interaction (D393A) were further characterized in authentic CHIKV and displayed attenuation consistent with that observed in SFV. In vivo, all three variants showed reduced pathogenicity in the SFV mouse model, with F164A being avirulent, immunogenic, and conferring complete protection against lethal challenge. In a CHIKV mouse model, these mutations attenuated disease and reduced serum virus titers and inflammatory cell infiltration. Together, these findings provide a molecular framework for the rational design of live-attenuated alphavirus vaccine candidates and support broader evaluation of nsP4-based attenuation. Alphaviruses are an increasing global health concern, with hundreds of thousands of chikungunya cases reported worldwide in 2025; however, vaccine options remain limited, and no specific antiviral treatment is available. Recent structural studies have revealed conserved functional interfaces in the viral RNA polymerase nsP4, but their value for attenuation had not been systematically explored. Here, using structure-guided mutagenesis, validation in multiple viral systems, and in vivo analysis, we show that selected nsP4 mutations can strongly attenuate replication and pathogenicity while preserving immunogenicity. These findings identify conserved nsP4 interfaces as a shared vulnerability of alphaviruses and provide a molecular framework for the rational design of broadly applicable live-attenuated vaccines while also highlighting nsP4 as a functionally constrained target relevant to antiviral development.
2026-08-26 | Chikungunya Vaccines in Travel Medicine: From Regulatory Approval to Real-World Challenges.
Background: Chikungunya virus (CHIKV) infection is an emerging disease of growing concern to international travelers due to the expanding geographic distribution of competent vectors, climate change, and frequent outbreaks in endemic and previously unaffected regions. Until recently, prevention relied exclusively on vector control and bite prevention; however, the recent approval of chikungunya vaccines has introduced a new preventive strategy. Methods: We conducted a narrative review of currently licensed chikungunya vaccines and candidates in clinical development, focusing on immunogenicity, safety, regulatory status, and implications for travel medicine practice. Results: Two vaccines have recently received regulatory approval: the live-attenuated vaccine IXCHIQ® and the virus-like particle vaccine Vimkunya®. Both demonstrated high immunogenicity based on neutralizing antibody thresholds accepted as surrogate markers of protection. Post-marketing safety signals associated with IXCHIQ®, particularly in older adults, have led to divergent regulatory decisions between authorities. The indication of vaccination in national recommendations varies somewhat depending on age, duration of travel, and individual risk factors. Several additional vaccine platforms remain under investigation, although some candidates have been discontinued. Conclusions: The recent approval of chikungunya vaccines marks a significant milestone in the field of travel medicine. However, uncertainties regarding long-term protection, safety in specific populations, and optimal targeting of travelers remain. Individualized risk-benefit assessment is essential, and further data are needed to refine vaccination strategies for travelers and populations at risk.
2026-08-13 | Antibodies elicited by a chimeric peritrophin antigen reduce Aedes aegypti survival after blood feeding.
Vector-borne diseases transmitted by Aedes aegypti, including dengue, Zika, chikungunya, and yellow fever, represent a persistent and expanding global health threat. Limitations of conventional vector control strategies, such as insecticide use and environmental source reduction, particularly in urban settings, underscore the need for novel and complementary tools. Anti-vector vaccination offers one such strategy by inducing host-derived antibodies that are ingested during vector feeding and interfere with vector physiology or survival. Although this concept has been successfully explored in some hematophagous arthropods, it remains largely unexplored in mosquitoes. Here, we investigated mosquito peritrophins, structural components of the midgut peritrophic matrix, as potential targets for vector-directed vaccination. We designed and recombinantly expressed a chimeric antigen, PT-3, incorporating immunogenic regions from three Aedes aegypti peritrophins/peritrophin-like proteins: AAEL002495, AAEL002467, and AAEL004798. The ability of PT-3 to elicit functional antibodies was evaluated in a bovine host model. Immunization induced a robust antigen-specific humoral response, and mosquitoes fed blood supplemented with immune sera from vaccinated animals showed significantly reduced post-feeding survival compared with controls. Consistent with this functional effect, anti-PT-3 immune sera recognized native mosquito midgut components in ELISA and Western blot assays. Overall, results are consistent with antibody-mediated interference with midgut physiological processes during blood digestion, while no significant effects on oviposition or egg viability were observed among surviving females. Together, these findings provide proof-of-concept that mosquito peritrophins can serve as immunological targets for anti-vector vaccination and provide a rationale for further developing peritrophin-targeted strategies, including alternative delivery platforms, as complementary tools for arboviral control.
2026-08-06 | Chikungunya vaccine approval in Brazil: navigating through epidemiological challenges and immunisation strategies.
Chikungunya virus (CHIKV) can cause acute arboviral illness, usually accompanied by severe polyarthralgia. In 2025, live-attenuated CHIKV vaccine Ixchiq® (Valneva, Saint-Herblain, France) was authorised for use in Brazil, where CHIKV often co-circulates with other arboviruses. A central public health question emerges: how should this vaccine be optimally deployed in a country characterised by hyperendemic transmission, frequent underdiagnosis, and marked regional disparities? We conducted an epidemiological analysis using notified CHIKV cases from the Notifiable Diseases Information System (SINAN) and socioeconomic indicators from the Brazilian Human Development Atlas. This framework enabled the identification of municipal clusters with shared epidemiological and socioeconomic profiles, allowing exploration of the relationship between disease notification rate and social health determinants. Our results showed that CHIKV transmission exhibited a cyclic pattern with geographic expansion toward the Southeast/South - Brazil's most densely populated regions characterised by low population immunity. Cluster analyses showed that the greatest disease burden is concentrated in socioeconomically disadvantaged municipalities, particularly in the Northeast, where healthcare disparities may further impact diagnostic capacity. Based on the obtained results, we believe in a hybrid immunisation strategy starting from high-incidence municipalities in the northeast and reaching major urban centres in the southeast in order to prevent larger outbreaks. Implementation must account also for current vaccine contraindications in high-risk groups and be guided by real-time epidemiological and entomological surveillance.
antibodies
2026-09-13 | Natural-killer-cell-mediated antibody-dependent cellular cytotoxicity response in acute and recovery phases of chikungunya.
Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is well documented in the clearance of various viral infections. Beyond direct virus neutralization, virus-specific antibodies confer protection through effector functions involving ADCC. NK cells have been identified as key contributors in chikungunya pathogenesis. This study evaluates NK cell-mediated ADCC involvement in chikungunya by assessing chikungunya virus (CHIKV)-specific ADCC responses in 56 acute, 56 prolonged, and 44 chronic chikungunya arthritis patients, 23 recovered individuals, and 50 healthy controls. A flow-cytometry-based antibody-dependent heterologous NK cell activation assay was employed, utilizing CD107a and IFN-γ as surrogate markers. Group comparisons were performed using the Mann-Whitney test, binary data were analyzed by Fisher's exact test, and correlations between ADCC response, CHIKV viral loads, total anti-CHIKV IgG, and IgG3 antibody levels were assessed by Spearman rank correlation. P values < 0.05 were considered significant. Persistence of ADCC response was observed in recovered individuals for durations ranging from 3 months to 18 years post-infection, while a progressive decline was noted in patients with chronic chikungunya arthritis. An inverse association between ADCC response and viral load was observed in a subset of acute patients. Recovered individuals demonstrated a positive correlation between ADCC response and plasma anti-CHIKV IgG and IgG3 antibody levels (IgG: r = 0.4503, IgG3: r = 0.4583, p-value < 0.01 for each). Collectively, these findings establish the role of NK cell-mediated ADCC response in chikungunya infection and provide a foundation for future antibody-based therapeutics for chikungunya, particularly utilizing IgG3 antibodies with functional ADCC capacity.
2026-08-20 | IL-17A Restrains Antiviral Immunity to Promote Chikungunya Virus Infection and Pathogenesis in the Heart.
Chikungunya virus (CHIKV) infection is increasingly linked to cardiovascular complications, but the mechanisms underlying CHIKV-induced cardiovascular disease (CVD) remain unclear, and targeted therapies are lacking. Although elevated interleukin-17A (IL-17A) levels have been reported in CHIKV patients and associated with cardiovascular pathology, its role in CHIKV-induced cardiac disease is poorly defined. To address this question, we employed our newly developed heterozygous interferon α/β/γ receptor-deficient ( Ifnag +/- ) mice and primary human cardiac fibroblasts to investigate the contribution of IL-17A signaling to CHIKV-associated cardiac pathology. We found that CHIKV infection induced IL-17A production in the heart, and that mice deficient in Il17a ( Il17a -/- ) and in its receptor gene, Il-17ra ( Il17ra -/- ), exhibited marked resistance to CHIKV infection in both cardiac tissue and primary cardiac fibroblasts. Genetic deletion of IL-17A signaling significantly enhanced type I interferon responses and decreased viral burden in mouse hearts. Interestingly, blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque psoriasis, Brodalumab, drastically increased type I interferon production and reduced viral replication in both human cardiac fibroblasts and human embryonic kidney 293 (HEK 293) cells. In addition, inhibition of IL-17A signaling suppressed the expression of pro-inflammatory mediators, including Il-1β , Tnf-α , and Cxcl2 , reduced immune cell infiltration into cardiac tissue, and mitigated cardiac injury. Importantly, therapeutic blockade of IL-17A signaling after CHIKV infection reduced viral replication in both the heart and circulation. Collectively, these findings identify IL-17A signaling as a critical regulator of CHIKV replication and cardiac inflammation and highlight the IL-17A/IL-17RA axis as a promising therapeutic target for CHIKV-associated cardiovascular disease. Chikungunya virus (CHIKV) infection has been frequently associated with cardiovascular complications, yet the host pathways that promote viral infection and cardiac injury remain poorly understood. Here, we identify IL-17A signaling as a previously unrecognized regulator of CHIKV pathogenesis in the heart. Using a novel heterozygous interferon receptor-deficient mouse model and primary human cardiac fibroblasts, we demonstrate that IL-17A signaling facilitates CHIKV replication via suppressing antiviral type I interferon responses. Genetic deletion or pharmacological blockade with an FDA-approved monoclonal antibody of IL-17A signaling reduced viral burden, attenuated inflammatory cytokine production, limited immune cell infiltration, and protected against cardiac injury. Importantly, therapeutic inhibition of IL-17A signaling after infection remained effective in reducing viral replication in both cardiac tissue and circulation and mitigating cardiac damage. These findings reveal a critical role for the IL-17A/IL-17RA axis in linking antiviral immunity to CHIKV-induced cardiovascular disease and identify a potential translatable therapeutic target for CHIKV-caused cardiac complications.
2026-05-23 | CONVICTION-CHIK study on the effect of convalescent plasma for mother-to-child Chikungunya infection: protocol for a multicentre, open label, single-arm, phase II trial.
Mother-to-child peripartum transmission of Chikungunya infection may induce severe illness with neonatal encephalitis/encephalopathy, leading to major neurological sequalae in offspring. There is not, at present, any licensed vaccine or treatment for Chikungunya virus (CHIKV) disease in pregnant women or neonates. However, there are a range of potential treatments, including passive immune therapies by hyperimmune antibodies or blood products, which warrant further investigation. Our study aims to determine whether the early administration of CHIKV convalescent plasma donor is effective in preventing several adverse outcomes in neonates exposed to maternal peripartum CHIKV infection. CONVICTION-CHIK is a multicentre, interventional, phase II, single-arm trial, that will be conducted in two French overseas departments in the Indian Ocean throughout 2026. Neonates with the following criteria will be included: (1) mother with a clinical and/or biological diagnosis of CHIKV infection occurring between day -2 and + 2 around delivery; (2) cared for in a 3rd level neonatal intensive care unit; (3) treatment administration possible within 12 h from diagnosis of maternal infection. The intervention consists in the transfusion of 25 mL/kg of ABO CHIKV convalescent plasma over 4 h. The primary endpoint is the proportion of newborn infants treated with CHIKV convalescent plasma who survive without encephalitis/encephalopathy in the first 5 days of life. This outcome will also be assessed in a parallel cohort of untreated newborn infants exposed to peripartum CHIKV infection. Secondary endpoints are clinical, biological, and brain imaging findings of neonatal CHIKV infection, in treated and untreated neonates. Based on an expected decrease in the primary endpoint from 25% to 3% in the intervention group, the required sample size is 30 treated neonates. A parallel cohort of 30 contemporaneous untreated neonates will be enrolled to provide exploratory context for the observed treatment effect. If successful, this research will expand the therapeutic arsenal for treating peripartum neonatal CHIKV infection, in addition to symptomatic management of organ failure. The results of this study will allow to consider the feasibility to implement the systematic collection of convalescent plasma following Chikungunya outbreaks, for the management of subsequent epidemics. NCT07190560 (registered 17 September 2025).
2026-03-25 | E2 Protein of Chikungunya Virus: A Narrative Review of Its Potential as a Therapeutic Target.
Chikungunya Virus (CHIKV), an enveloped RNA virus transmitted by Aedes mosquitoes, has become an increasing global health concern, particularly in South America, where cases and fatalities have risen (PAHO, 2023). This review focuses on therapeutic strategies targeting the CHIKV E2 protein, including vaccines, antibodies, and antiviral approaches tested in vitro and in vivo. Literature reporting on the E2 protein, including studies on viral structure, host interactions, symptoms, and treatments under development, was analyzed. The E2 protein, a major structural component of CHIKV, is critical for viral entry and virulence, mediating interactions with host factors (Glycosaminoglycans (GAGs) and C-type lectins) and receptors (Matrix Remodeling-Associated Protein 8 (Mxra8) and Prohibitin-1 (PHB1)). It also elicits robust antibody responses, making it a key target for therapeutic intervention. The E2 protein is essential for CHIKV entry and virulence, making it a key target for vaccines, antibodies, and antivirals. While preclinical studies show promise, efficacy varies and clinical translation remains limited. Challenges include viral diversity, immune escape, and the need for integrated strategies combining different therapeutic approaches. Given the absence of licensed vaccines and antivirals for alphaviruses, the E2 protein represents a promising therapeutic target while inhibiting E2 could block viral entry and infection. However, current strategies show variable efficacy and inconclusive results, highlighting the need for further research to validate and optimize E2-targeted therapies.
2026-01-29 | Human autoantibodies against type I interferons in severe viral disease.
Type I interferons (IFN-Is) are critical antiviral cytokines that restrict viral replication and limit viral disease. A remarkable recent discovery is that human autoantibodies (autoAbs) neutralizing the activities of IFN-Is phenocopy inborn errors of immunity and markedly exacerbate susceptibility to life-threatening infections. Development of these pathogenic autoAbs in humans is strongly linked to genetic and nongenetic factors affecting thymic function, and they are estimated to be present in >100 million people worldwide with a prevalence that increases with age. Here, we review major advances from the last few years that have improved our mechanistic understanding of human IFN-I autoAb development and function, as well as their association with a significant proportion of different severe viral diseases. In particular, we highlight how neutralizing IFN-I autoAbs can persist in individuals for decades, compromising IFN-I-mediated defenses, and underlying subsequent critical infections with diverse pathogens, including SARS-CoV-2, West Nile virus, tick-borne encephalitis virus, seasonal influenza viruses, herpesviruses, and rare zoonoses caused by MERS-CoV, flaviviruses, and avian H5N1 influenza A virus. Furthermore, we discuss how neutralizing IFN-I autoAbs facilitate severe adverse events with live-attenuated viral vaccines, such as the yellow fever or chikungunya virus vaccines, and suggest how implementation of IFN-I autoAb diagnostics in at-risk populations may be clinically beneficial with current prophylactic or therapeutic options. Finally, in the context of new experimental insights into how autoAbs block the ability of IFN-Is to engage with the IFNAR1/IFNAR2 receptors, we detail future opportunities to design advanced novel therapeutic strategies that might specifically mitigate IFN-I autoAb pathogenic effects.
other
2026-09-26 | Chikungunya Virus E2 N218K Enhances Heparan Sulfate-Dependent Attachment and Viral Internalization While Conferring Partial Attenuation in A129 Mice.
The E2 glycoprotein of chikungunya virus (CHIKV) binds negatively charged cell-surface heparan sulfate (HS) to facilitate viral attachment and modulate pathogenicity, yet the E2 determinants governing HS-dependent attachment and the effects of altered HS utilization on subsequent infection remain incompletely defined. From a low-passage clinical isolate obtained during the 2010 Guangdong outbreak, we identified a previously unreported E2 substitution, N218K, which introduces a basic residue. In vitro, this mutation enhanced early infection and attachment to mammalian cells and reduced the RNA/PFU ratio; in A129 mice, however, it reduced early serum viral RNA levels, was associated with lower tissue viral RNA burdens at 5 dpi, and delayed mortality, consistent with partial attenuation. Soluble HS competition assays showed that N218K increased HS dependence during viral attachment, whereas DEAE-dextran assays supported a role for charge-dependent interactions in restricting local viral spread. N218K also enhanced viral internalization after normalization of initial attachment, identifying an additional post-attachment phenotype associated with this substitution. Our findings identify N218K as a determinant of HS-dependent attachment and partial attenuation in A129 mice, reveal a "high attachment-low dissemination" phenotype, and further show that this charge-altering E2 substitution enhances post-attachment internalization.
2026-09-14 | A Restriction-Free Cloning Approach for Molecular Engineering of Plasmids.
Molecular cloning by PCR amplification using a highly processive, high-fidelity DNA polymerase represents a robust and versatile technique for the precise manipulation of nucleic acid sequences. This approach enables the insertion, replacement, or modification of specific DNA fragments within a cloning vector, thereby generating an accurate copy of a gene or viral segment for downstream applications, such as protein expression, site-directed mutagenesis, and structural or functional analyses. The use of processive, high-fidelity polymerases significantly reduces the occurrence of base substitution errors, ensuring sequence integrity throughout the amplification process. Traditionally, restriction enzymes have been employed to facilitate directional cloning; however, alternative methods allow for mutagenesis without the need for unique and specific restriction sites and can be applied to virtually any cloning or seamless DNA assembly strategy. In this chapter, we describe a restriction enzyme-free and ligation-free PCR-based protocol widely applicable to any circular vector. This method enables targeted mutagenesis of the chikungunya virus (CHIKV) genome, offering a fast, efficient, and reliable strategy for generating mutant constructs suitable for virological and molecular studies.
2026-08-28 | Effects of different X-ray irradiation dosages on Wolbachia trans-infected and uninfected Aedes aegypti mosquitoes.
Aedes aegypti is a primary vector of several arboviral diseases, including dengue, chikungunya, Zika, and yellow fever. Eliminating Ae. aegypti can disrupt virus transmission cycles, thereby reducing the incidence of these diseases. Releasing sterile Ae. aegypti males has been implemented to suppress their natural populations, using three approaches, i.e., ionizing radiation-induced sterilization (Sterile Insect Technique, SIT), Wolbachia-induced cytoplasmic incompatibility (Incompatible Insect Technique, IIT), and a combination of both approaches (SIT/IIT). This study investigated effects of different X-ray radiation doses on the ecological fitness of the Thai wild-type and Wolbachia trans-infected Ae. aegypti. Both wild-type and wAlbB trans-infected Ae. aegypti were irradiated with different X-ray radiation dosages, i.e., 30, 50, and 70 Gy, at the pupal stage. Our results demonstrated reduced fitness parameters in both Ae. aegypti strains when irradiation dosages increased, with greater adverse effects observed in the Wolbachia-infected group. Interestingly, 30 Gy irradiation appeared to prolong the lifespan of wAlbB trans-infected Ae. aegypti. Male fertility in both wild-type and wAlbB trans-infected mosquitoes irradiated at 50 Gy and 70 Gy was nearly zero. Wolbachia density generally declined with increasing radiation, and higher doses were associated with reduced mating competitiveness. At 30 Gy, wild-type males outperformed wAlbB trans-infected males in mating competitiveness; but it was reversed at 50 Gy and 70 Gy. Based on the evaluation of ecological fitness parameters and mating competitiveness across various X-ray dosages under laboratory conditions, 30 Gy is recommended for sterilizing both Thai wild-type and wAlbB trans-infected Ae. aegypti. Our findings aim to improve the efficiency of sterile mosquito release programs, thereby suppressing Ae. aegypti vector populations and mitigating the risk of arboviral disease transmission.
2026-07-28 | Single-stranded nucleic acid binding enhances the in vitro catalytic activity of Chikungunya virus nsP2 protease.
Chikungunya virus (CHIKV) is an emerging arbovirus whose replication relies on the multifunctional nonstructural protein 2 (nsP2), particularly its viral protease (nsP2pro), which is essential for polyprotein processing. In this study, we investigated how interactions with nucleic acids influence nsP2pro activity. Using High-Throughput Sequencing-Fluorescent Ligand Interaction Profiling (HiTS-FLIP), we identified specific single-stranded DNA aptamers that enhanced nsP2pro activity. Additionally, both random single-stranded DNA and single-stranded RNA were found to stimulate protease activity, whereas double-stranded DNA showed no such effect. Circular dichroism spectroscopy and secondary structure predictions confirmed that the identified aptamers adopt stable folded conformations. Similarly, structured RNA sequences were also capable of promoting protease activity. The observed stimulatory effect depended on the nucleic acid strand type, length, and buffer conditions, suggesting the involvement of electrostatic interactions. NMR experiments demonstrated that nsP2pro interacts with single-stranded DNA, accompanied by changes in its conformational dynamics upon binding. Molecular dynamic simulations of nsP2pro-RNA and -DNA complexes revealed that these nucleic acids interact specifically with the nsP2pro methyltransferase domain and induce an opening process in the protease active site. Our findings provide novel insights into the regulation of nsP2pro, enhancing our understanding of CHIKV replication mechanisms, and may guide future antiviral development strategies.
2026-05-24 | Aptamers as immunomodulatory therapeutic alternatives targeting neglected tropical diseases (NTDs).
Neglected tropical diseases (NTDs) comprise a heterogeneous group of infections that disproportionately affect populations in low- and middle-income countries, where limited access to diagnostics, therapeutics, and surveillance perpetuates disease burden. Conventional strategies based on antibodies and small-molecule drugs face major challenges, including high production costs, limited stability, cross-reactivity, toxicity, and the emergence of drug resistance. In this context, aptamers, short single-stranded nucleic acids selected by SELEX, have emerged as versatile immunomodulatory tools with significant potential for the diagnosis and treatment of NTDs. This chapter provides a comprehensive overview of aptamer-based strategies targeting major NTDs, with particular emphasis on human African trypanosomiasis and arboviral infections such as dengue, Zika, and chikungunya. Aptamers directed against conserved parasite and viral epitopes demonstrate the capacity to circumvent immune evasion mechanisms, including antigenic variation and serotype diversity, while enabling highly specific recognition and internalization. In African trypanosomes, RNA aptamers targeting variant surface glycoproteins exploit the flagellar pocket for targeted drug delivery, offering a novel approach to overcome therapeutic resistance. In arboviral diseases, aptamers have been successfully integrated into advanced diagnostic platforms, including competitive ELISA, electrochemical, and capacitive biosensors, achieving high sensitivity, rapid response times, and minimal cross-reactivity among closely related flaviviruses. Beyond diagnostics, selected aptamers exhibit neutralizing activity and immunomodulatory effects by interfering with host-pathogen interactions and innate immune signaling pathways.
proteins
2026-09-06 | Scorpion Peptides in Antiviral Drug Discovery: An In-depth Review.
Despite remarkable progress in the fields of vaccinology and antiviral therapy, viral infections persist as a leading cause of morbidity and mortality worldwide. Therefore, it is crucial to identify new and effective antiviral drug candidates. Scorpion venoms are viewed as a rich source of structurally diverse and biologically active peptides, which may present opportunities for diagnostic, preventive, and therapeutic applications. This review intends to provide a contemporary and detailed analysis of scorpion-derived peptides, with a particular focus on their structural diversity, cytotoxic effects, antiviral properties, and mechanisms of action. Additionally, this paper highlights several potential fruitful areas for future studies. Current evidence indicates that scorpion-derived peptides are effective against a wide array of medically important viral pathogens such as chikungunya virus, dengue virus, enterovirus 71, hepatitis B virus (HBV), herpes simplex virus 1, human immunodeficiency virus 1, influenza A virus (IAV), severe acute respiratory syndrome coronavirus-2, and Zika virus. Nevertheless, the majority of these findings have been obtained from in vitro studies, whereas evidence from animal models remains limited and clinical evaluation in humans is currently unavailable. Available studies suggest that these peptides may act through diverse mechanisms of action, including direct virucidal activity, inhibition of viral entry, immune system modulation, reduction of virus-induced cytopathic effects, and suppression of viral gene expression. Emerging evidence also demonstrates the efficacy of certain scorpion-derived peptides in animal models of HBV, IAV, and Newcastle disease virus infection. Overall, such peptides appear to inaugurate new avenues for the treatment of viral infections.
2026-08-20 | Lachesin is a mosquito receptor for multiple arthritogenic alphaviruses.
Arthritogenic alphaviruses cause acute febrile illnesses associated with rash and arthritis when they are transmitted to humans through the bite of infected mosquitoes. Among these, chikungunya virus (CHIKV), transmitted primarily through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes, causes explosive outbreaks involving hundreds of thousands to millions of cases, with recent re-emergence in several global regions. While several cellular receptors that mediate alphavirus entry into mammalian cells have been identified, their mosquito counterparts remained unknown, largely due to a lack of functional genomics tools for these invertebrate species. Here, we established a CRISPR-based genetic screening platform in Aedes albopictus cells and used it to identify Lachesin, a conserved invertebrate cell adhesion molecule, as a receptor for CHIKV and multiple related alphaviruses including Semliki Forest virus (SFV), o'nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). Lachesin depletion using RNA interference, anti-Lachesin antibody treatment, and soluble forms of Lachesin blocked CHIKV and SFV E2-E1 glycoprotein-mediated infection of mosquito cells. We show that alphavirus E2-E1 glycoproteins bind the first immunoglobulin domain of Lachesin, facilitating attachment and internalization of virus-like particles. Orthologs from divergent mosquito genera, but not from arachnids or other arthropods, also serve as alphavirus receptors, suggesting that cellular receptor binding is not the main obstacle to arthritogenic alphavirus vector host expansion. Our findings enhance understanding of the mechanisms of alphavirus emergence and vector competence and could aid in the development of broadly active, entry-targeted therapeutics against multiple alphaviruses that threaten public health.
2026-08-20 | Molecular basis for chikungunya virus recognition of a mosquito-specific receptor.
Alphaviruses are arthropod-borne viruses that recognize cellular receptors in both vertebrate hosts and mosquito vectors to complete their transmission cycle, yet how they maintain recognition of receptors across evolutionarily divergent host species remains unresolved. Among alphaviruses, chikungunya virus (CHIKV), which is primarily vectored in urban settings by Aedes species mosquitoes, is the most widespread, and causes explosive outbreaks that can involve hundreds of thousands to millions of cases annually. The cell adhesion protein Lachesin is a mosquito-specific cellular receptor for CHIKV and multiple other arthritogenic alphaviruses. The envelope E2-E1 glycoproteins of these alphaviruses broadly recognize Lachesin orthologs from diverse mosquito species, but not other insects or arachnids. Lachesin genetic manipulation to prevent mosquito virus infection without interfering with endogenous receptor function could have a major impact for CHIKV control. Here, we determined high-resolution cryo-electron microscopy (cryo-EM) structures of alphaviruses bound to Aedes albopictus Lachesin. Comparative analysis of Lachesin-bound CHIKV, Semliki Forest virus (SFV), and Middelburg virus (MIDV) revealed that these three genetically divergent viruses use a similar surface to recognize Lachesin domain 1, but with reorganized E2-E1 glycoprotein contact residues. We show that a soluble Ae. albopictus Lachesin receptor decoy protein blocks the E2-E1-mediated entry of CHIKV and other arthritogenic alphaviruses into mammalian cells with greater breadth than a vertebrate receptor MXRA8 decoy and protects against lethal SFV challenge and CHIKV pathogenesis in murine models. Additionally, we identified a naturally occurring single residue Lachesin polymorphism that is found in some Anopheles (malaria vector) mosquitoes, and fully ablates CHIKV E2-E1 recognition, informing strategies for mosquito-targeted genetic interventions that could prevent mosquito vector infection and virus transmission. These findings define distinct determinants of receptor binding in mosquitoes and humans for arthritogenic alphaviruses, with implications for countermeasure development and outbreak preparedness.
2026-07-28 | Low-Dose Interleukin-2 Enhances Activated Suppressor Regulatory T Cells and CTLA-4 and HLA-DR Expression in Chronic Chikungunya Arthritis.
Chronic chikungunya arthritis is a debilitating post-viral inflammatory arthritis with no established evidence-based therapy. Regulatory T cell (Treg) dysfunction may contribute to persistent inflammation, and low-dose interleukin-2 (IL-2) may restore immune regulation. We evaluated the immunomodulatory effects of low-dose IL-2 using peripheral blood mononuclear cells from adults with laboratory-confirmed chronic chikungunya arthritis in Atlántico, Colombia. Cells were treated ex vivo with recombinant IL-2 or an IL-2/anti-IL-2 monoclonal antibody complex in the presence of CD2/CD3/CD28 stimulation beads, followed by flow cytometric assessment of effector T cells and Tregs. Low-dose IL-2 treatments ex vivo did not increase total Treg frequency but selectively increased activated suppressor Tregs while decreasing activated T effector cells, enhancing Treg CTLA-4 and HLA-DR expression, and reducing Ki67 expression in effector T cells. IL-2 complex treatment decreased cytokine-secreting Tregs, and IL-10 and TGF-β were not associated with IL-2 treatment status or with Teff/Treg balance, suggesting limited utility as pharmacodynamic biomarkers of low-dose IL-2 treatments. These findings support the use of activated suppressor Tregs, Treg CTLA-4, and HLA-DR expression as candidate biologic endpoints for evaluation in future trials of low-dose IL-2 in chikungunya arthritis.
2026-07-21 | Ewing sarcoma breakpoint region 1 (EWSR1) protein binds to nonstructural protein 2 and non-coding regions of chikungunya virus genome to inhibit virus replication.
Chikungunya virus (CHIKV) is an alphavirus with a single-stranded RNA genome. Conserved sequence elements within the 5' and 3' non-coding regions (NCRs) of the CHIKV genome interact with host proteins to regulate viral RNA replication. Electrophoretic mobility shift assays (EMSAs) and mass spectrometry identified several host RNA-binding proteins that associate with these conserved NCR elements, among which EWSR1 uniquely bound the 3' ends of both the plus-sense genomic RNA and the minus-sense replication intermediate RNA. EMSA and biolayer interferometry (BLI) demonstrated that EWSR1 binds strongly to two RNA elements: a 48-nucleotide region in the plus-strand 3'-NCR (3NCR48) and a 50-nucleotide region at the 3'-end of the minus-strand replication intermediate (5NCR-RC50), which is complementary to the genome's 5'-NCR and its adjacent sequence. RNA immunoprecipitation from CHIKV-infected cells confirmed that EWSR1 binds CHIKV RNA in vivo. Functional analyses revealed that CHIKV infection downregulates EWSR1 expression and causes its accumulation in the cytoplasm. Knockdown or knockout (KO) of EWSR1 expression increased CHIKV genomic RNA levels and viral titers, whereas its overexpression suppressed both. EWSR1 reduced the synthesis of both plus- and minus-sense CHIKV RNAs in infected cells. Additionally, EWSR1 was found to bind to CHIKV nsP2 and inhibit its helicase activity, which is critical for viral genome replication. The antiviral activity of EWSR1 extended to Ross River virus but not to Sindbis virus, consistent with conservation of the 48-nucleotide sequence in their respective 3'-NCRs. Together, these findings identify EWSR1 as a novel host restriction factor that limits CHIKV replication through specific interactions with viral RNA and the nsP2 protein.IMPORTANCEChikungunya virus (CHIKV) poses a significant medical challenge, necessitating the development of novel antiviral strategies. This study demonstrates that the host protein EWSR1 plays a key role in controlling CHIKV replication. By binding to specific regions of viral RNA and interacting with nsP2, a critical viral enzyme, EWSR1 inhibits viral RNA synthesis and reduces viral titers. In the absence of EWSR1, CHIKV replicates more efficiently, underscoring its antiviral function. These findings establish EWSR1 as an important host restriction factor that limits CHIKV replication. Understanding this interaction enhances our knowledge of host-virus dynamics and may guide the design of new antiviral approaches against CHIKV and related alphaviruses.
small molecules
2026-09-30 | Neuropilin-1 functions as a proviral and immunoregulatory host factor during Chikungunya virus infection.
Neuropilin-1 (NRP1) is a transmembrane glycoprotein involved in angiogenesis, neurodevelopment, inflammation, cancer driven immune suppression, and immune homeostasis. However, its contribution to virus-induced immune responses is not explored. Chikungunya virus (CHIKV) is a re-emerging arthritogenic alphavirus that causes severe arthralgia, and myalgia, accompanied by heightened inflammatory cytokine responses. The host factors that drive these inflammatory responses, however, remain poorly defined. Here, in this current study, the role of NRP1 in CHIKV infection was investigated using in vitro , and in vivo model systems. Using genetic manipulation, pharmacological, and antibody blockade-mediated approaches in murine and human cellular infection models, it was demonstrated that NRP1 promotes CHIKV infection while restraining the production of proinflammatory cytokines. Furthermore, NRP1 inhibition selectively increased JNK phosphorylation. Hence, inhibiting JNK reduced the elevated cytokine production caused by NRP1 blockade. Moreover, NRP1 interacted with CHIKV-E1 and is involved in multiple phases of CHIKV infection. In addition, it was demonstrated that NRP1 inhibition using EG00229 trifluoroacetate can reduce viral infection in several CHIKV-susceptible cells, human peripheral blood macrophages, and in the in vivo mice model of infection. Together, these findings indicate that NRP1 is an important host factor and a probable therapeutic target during CHIKV infection. Chikungunya virus (CHIKV) causes acute febrile illness that can progress to debilitating chronic musculoskeletal and occasional neurological complications. The absence of a globally available effective vaccine and the lack of specific antivirals underscore CHIKV as a major burden, especially in endemic tropical regions. There is a growing need to understand host factors that shape CHIKV-driven immune response. The importance of our study lies in understanding the immunoregulatory role of the host receptor Neuropilin-1 (NRP1) during CHIKV infection. We identify NRP1 as a novel host factor of CHIKV infection that also acts as a rheostat to restrict the inflammatory viral immune response. Moreover, we report anti-viral potential of the NRP1 antagonist EG00229 trifluoroacetate in multiple cell lines, primary cells, and mice model. Our findings indicate NRP1 as a probable therapeutic target in CHIKV pathogenesis.
2026-09-26 | Synthesis and Broad-Spectrum Antiviral Evaluation of Novel 1,2,3-Triazole-Quinoline Derivatives Targeting SARS-CoV-2, Influenza, DENV-2, and CHIKV.
The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole-quinoline derivatives (compounds 4a-4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a-4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens.
2026-09-25 | Backs under pressure: measuring and estimating lumbar spinal loads.
This issue of the Biomedical Journal examines lumbar spinal loading and current approaches to its assessment using invasive measurements, biomechanical modeling, imaging, wearable technologies, and AI-assisted methods. Other contributions address coumarin derivatives as modulators of autophagy and PI3K/mTOR signaling in cancer and apply multi-omics approaches to uric acid metabolism and cardiometabolic disease. Further studies investigate molecular mechanisms linking mechanical irritation to oral squamous cell carcinoma progression, predictors of HBsAg seroclearance after antiviral treatment withdrawal, and age-dependent effects of exercise and losartan. Additional contributions explore PD-L1 signaling in allergic asthma, the antiviral activity of BPR2-D2 against chikungunya virus replication, and differences in objective tear function between patients with and without mental disorders.
2026-09-15 | Solanaceae-Derived Spirostane Saponins Inhibit Dengue Virus Replication and Viral Protein Expression and Exhibit Activity Against Multiple Arboviruses.
Mosquito-borne arboviruses, including dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV), represent a growing global health burden, yet no specific antiviral therapies are currently available for most of these infections. This unmet need highlights the importance of identifying novel antiviral compounds from biologically relevant sources such as plant-derived natural products. In this study, a bioactivity-guided approach was applied to methanolic extracts from eight Solanaceae species to identify compounds with antiviral activity against DENV-2 in Vero cells. Five extracts significantly reduced viral infectivity, with Solanum ovalifolium and Cestrum sp. achieving complete inhibition at non-cytotoxic concentrations. Subsequent fractionation and purification led to the isolation of four spirostane-type steroidal saponins, structurally characterized by UPLC-DAD-MS and 1D/2D NMR spectroscopy. Functional assays demonstrated that these compounds inhibit DENV replication, as evidenced by marked reductions in viral RNA levels, NS1 and NS3 protein expression, and infectious viral titers. Stage-specific analyses revealed that their antiviral activity is primarily associated with intracellular phases of the viral life cycle, consistent with inhibition of viral replication and/or protein processing. Molecular docking analyses supported these findings by predicting favorable interactions with key viral enzymes, particularly NS5 RNA-dependent RNA polymerase and NS3 helicase/protease. Importantly, the isolated compounds retained antiviral activity against ZIKV and CHIKV, indicating cross-arboviral efficacy. Together, these findings identify spirostane saponins as promising antiviral scaffolds and support their further development as broad-spectrum antiviral agents.
2026-09-14 | Assessing Chikungunya Virus Protease Activity and Pharmacological Inhibition Using the acc-CHIK15-dnp Fluorogenic Peptide Substrate.
Chikungunya virus, a mosquito-borne alphavirus, poses a significant global health threat due to its rapid spread and lack of approved antiviral therapies. The viral nonstructural protein 2 protease (nsP2p) plays a critical role in processing the viral polyprotein to produce key viral enzymes, making it an attractive target for drug development. In this study, we describe the expression and purification of recombinant CHIKV nsP2 protease and establish a robust fluorogenic assay to measure its enzymatic activity using the acc-CHIK15-dnp peptide substrate. The assay enables real-time monitoring of proteolytic cleavage and provides a platform for evaluating small-molecule inhibitors. We present optimized conditions for protein expression in E. coli, affinity purification, and tag removal, achieving high-purity nsP2 protease suitable for biochemical characterization. Using this system, we also provide a robust protocol for determining IC₅₀ values for candidate inhibitors. This work provides a reproducible methodology for high-throughput screening of CHIKV protease inhibitors, facilitating the discovery of potential antiviral compounds against chikungunya virus.
vaccines
2026-09-16 | Development of a potential vaccine against dengue and chikungunya virus co-infection using immunoinformatics and structural evaluation.
Dengue virus (DENV) and chikungunya virus (CHIKV) co-infection poses a growing challenge in regions where both arboviruses co-circulate, highlighting the need for integrated vaccine strategies. Here, we designed a multi-epitope subunit vaccine candidate targeting conserved regions of the DENV NS1 protein and the CHIKV NSP1 protein using an immunoinformatics-based approach. Conserved CTL, HTL, and B-cell epitopes were selected on the basis of antigenicity, safety-related screening, and population coverage, then assembled with immunologically appropriate linkers and an N-terminal human β-defensin-2 adjuvant. The construct displayed favourable physicochemical features and acceptable structural quality after three-dimensional modeling and validation. Docking analysis indicated stable interaction with human TLR4, which was further examined by normal-mode analysis and 100-ns all-atom molecular dynamics simulations performed in AMBER v24 with the ff19SB force field. Trajectory analyses supported conformational stability of the vaccine-TLR4 complex, and MM/GBSA calculations suggested favourable binding energetics. Codon optimization supported expression feasibility in the E. coli pET-28a(+) system. In silico immune simulation further predicted induction of both humoral and cellular immune responses, with increased antibody production and immune-memory development. These results support the proposed construct as a rational candidate for further experimental evaluation toward a vaccine strategy against DENV-CHIKV co-infection.
2026-09-10 | Targeting conserved interaction surfaces of alphavirus nsP4 supports the rational design of live-attenuated vaccine candidates.
Alphaviruses are emerging arboviruses that pose a growing threat to global public health; however, effective interventions remain limited. Recent structural studies of the chikungunya virus (CHIKV) replicase core revealed that the viral RNA-dependent RNA polymerase nsP4 interacts with both nsP1 and nsP2 and is predicted to engage viral RNA. The conservation and multifunctionality of nsP4 make it a challenging but promising target for rational attenuation. Here, we evaluated 58 structure-guided mutations in nsP4 predicted to disrupt interactions with nsP1, nsP2, or viral RNA using a trans-replicase system. Sixteen selected mutations were further analyzed in a CHIKV-o'nyong-nyong virus chimera and Semliki Forest virus (SFV). Most mutants were viable but showed varying degrees of attenuation in mammalian and mosquito cells. Viruses carrying mutations in predicted RNA-interaction sites frequently acquired pseudoreversions and/or second-site compensatory changes, whereas those harboring mutations affecting nsP1 or nsP2 interfaces were more genetically stable. Three substitutions representing defects in nsP1 interaction (F164A), predicted RNA interaction (K174S), and nsP2 interaction (D393A) were further characterized in authentic CHIKV and displayed attenuation consistent with that observed in SFV. In vivo, all three variants showed reduced pathogenicity in the SFV mouse model, with F164A being avirulent, immunogenic, and conferring complete protection against lethal challenge. In a CHIKV mouse model, these mutations attenuated disease and reduced serum virus titers and inflammatory cell infiltration. Together, these findings provide a molecular framework for the rational design of live-attenuated alphavirus vaccine candidates and support broader evaluation of nsP4-based attenuation. Alphaviruses are an increasing global health concern, with hundreds of thousands of chikungunya cases reported worldwide in 2025; however, vaccine options remain limited, and no specific antiviral treatment is available. Recent structural studies have revealed conserved functional interfaces in the viral RNA polymerase nsP4, but their value for attenuation had not been systematically explored. Here, using structure-guided mutagenesis, validation in multiple viral systems, and in vivo analysis, we show that selected nsP4 mutations can strongly attenuate replication and pathogenicity while preserving immunogenicity. These findings identify conserved nsP4 interfaces as a shared vulnerability of alphaviruses and provide a molecular framework for the rational design of broadly applicable live-attenuated vaccines while also highlighting nsP4 as a functionally constrained target relevant to antiviral development.
2026-08-26 | Chikungunya Vaccines in Travel Medicine: From Regulatory Approval to Real-World Challenges.
Background: Chikungunya virus (CHIKV) infection is an emerging disease of growing concern to international travelers due to the expanding geographic distribution of competent vectors, climate change, and frequent outbreaks in endemic and previously unaffected regions. Until recently, prevention relied exclusively on vector control and bite prevention; however, the recent approval of chikungunya vaccines has introduced a new preventive strategy. Methods: We conducted a narrative review of currently licensed chikungunya vaccines and candidates in clinical development, focusing on immunogenicity, safety, regulatory status, and implications for travel medicine practice. Results: Two vaccines have recently received regulatory approval: the live-attenuated vaccine IXCHIQ® and the virus-like particle vaccine Vimkunya®. Both demonstrated high immunogenicity based on neutralizing antibody thresholds accepted as surrogate markers of protection. Post-marketing safety signals associated with IXCHIQ®, particularly in older adults, have led to divergent regulatory decisions between authorities. The indication of vaccination in national recommendations varies somewhat depending on age, duration of travel, and individual risk factors. Several additional vaccine platforms remain under investigation, although some candidates have been discontinued. Conclusions: The recent approval of chikungunya vaccines marks a significant milestone in the field of travel medicine. However, uncertainties regarding long-term protection, safety in specific populations, and optimal targeting of travelers remain. Individualized risk-benefit assessment is essential, and further data are needed to refine vaccination strategies for travelers and populations at risk.
2026-08-13 | Antibodies elicited by a chimeric peritrophin antigen reduce Aedes aegypti survival after blood feeding.
Vector-borne diseases transmitted by Aedes aegypti, including dengue, Zika, chikungunya, and yellow fever, represent a persistent and expanding global health threat. Limitations of conventional vector control strategies, such as insecticide use and environmental source reduction, particularly in urban settings, underscore the need for novel and complementary tools. Anti-vector vaccination offers one such strategy by inducing host-derived antibodies that are ingested during vector feeding and interfere with vector physiology or survival. Although this concept has been successfully explored in some hematophagous arthropods, it remains largely unexplored in mosquitoes. Here, we investigated mosquito peritrophins, structural components of the midgut peritrophic matrix, as potential targets for vector-directed vaccination. We designed and recombinantly expressed a chimeric antigen, PT-3, incorporating immunogenic regions from three Aedes aegypti peritrophins/peritrophin-like proteins: AAEL002495, AAEL002467, and AAEL004798. The ability of PT-3 to elicit functional antibodies was evaluated in a bovine host model. Immunization induced a robust antigen-specific humoral response, and mosquitoes fed blood supplemented with immune sera from vaccinated animals showed significantly reduced post-feeding survival compared with controls. Consistent with this functional effect, anti-PT-3 immune sera recognized native mosquito midgut components in ELISA and Western blot assays. Overall, results are consistent with antibody-mediated interference with midgut physiological processes during blood digestion, while no significant effects on oviposition or egg viability were observed among surviving females. Together, these findings provide proof-of-concept that mosquito peritrophins can serve as immunological targets for anti-vector vaccination and provide a rationale for further developing peritrophin-targeted strategies, including alternative delivery platforms, as complementary tools for arboviral control.
2026-08-06 | Chikungunya vaccine approval in Brazil: navigating through epidemiological challenges and immunisation strategies.
Chikungunya virus (CHIKV) can cause acute arboviral illness, usually accompanied by severe polyarthralgia. In 2025, live-attenuated CHIKV vaccine Ixchiq® (Valneva, Saint-Herblain, France) was authorised for use in Brazil, where CHIKV often co-circulates with other arboviruses. A central public health question emerges: how should this vaccine be optimally deployed in a country characterised by hyperendemic transmission, frequent underdiagnosis, and marked regional disparities? We conducted an epidemiological analysis using notified CHIKV cases from the Notifiable Diseases Information System (SINAN) and socioeconomic indicators from the Brazilian Human Development Atlas. This framework enabled the identification of municipal clusters with shared epidemiological and socioeconomic profiles, allowing exploration of the relationship between disease notification rate and social health determinants. Our results showed that CHIKV transmission exhibited a cyclic pattern with geographic expansion toward the Southeast/South - Brazil's most densely populated regions characterised by low population immunity. Cluster analyses showed that the greatest disease burden is concentrated in socioeconomically disadvantaged municipalities, particularly in the Northeast, where healthcare disparities may further impact diagnostic capacity. Based on the obtained results, we believe in a hybrid immunisation strategy starting from high-incidence municipalities in the northeast and reaching major urban centres in the southeast in order to prevent larger outbreaks. Implementation must account also for current vaccine contraindications in high-risk groups and be guided by real-time epidemiological and entomological surveillance.
antibodies
2026-09-13 | Natural-killer-cell-mediated antibody-dependent cellular cytotoxicity response in acute and recovery phases of chikungunya.
Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is well documented in the clearance of various viral infections. Beyond direct virus neutralization, virus-specific antibodies confer protection through effector functions involving ADCC. NK cells have been identified as key contributors in chikungunya pathogenesis. This study evaluates NK cell-mediated ADCC involvement in chikungunya by assessing chikungunya virus (CHIKV)-specific ADCC responses in 56 acute, 56 prolonged, and 44 chronic chikungunya arthritis patients, 23 recovered individuals, and 50 healthy controls. A flow-cytometry-based antibody-dependent heterologous NK cell activation assay was employed, utilizing CD107a and IFN-γ as surrogate markers. Group comparisons were performed using the Mann-Whitney test, binary data were analyzed by Fisher's exact test, and correlations between ADCC response, CHIKV viral loads, total anti-CHIKV IgG, and IgG3 antibody levels were assessed by Spearman rank correlation. P values < 0.05 were considered significant. Persistence of ADCC response was observed in recovered individuals for durations ranging from 3 months to 18 years post-infection, while a progressive decline was noted in patients with chronic chikungunya arthritis. An inverse association between ADCC response and viral load was observed in a subset of acute patients. Recovered individuals demonstrated a positive correlation between ADCC response and plasma anti-CHIKV IgG and IgG3 antibody levels (IgG: r = 0.4503, IgG3: r = 0.4583, p-value < 0.01 for each). Collectively, these findings establish the role of NK cell-mediated ADCC response in chikungunya infection and provide a foundation for future antibody-based therapeutics for chikungunya, particularly utilizing IgG3 antibodies with functional ADCC capacity.
2026-08-20 | IL-17A Restrains Antiviral Immunity to Promote Chikungunya Virus Infection and Pathogenesis in the Heart.
Chikungunya virus (CHIKV) infection is increasingly linked to cardiovascular complications, but the mechanisms underlying CHIKV-induced cardiovascular disease (CVD) remain unclear, and targeted therapies are lacking. Although elevated interleukin-17A (IL-17A) levels have been reported in CHIKV patients and associated with cardiovascular pathology, its role in CHIKV-induced cardiac disease is poorly defined. To address this question, we employed our newly developed heterozygous interferon α/β/γ receptor-deficient ( Ifnag +/- ) mice and primary human cardiac fibroblasts to investigate the contribution of IL-17A signaling to CHIKV-associated cardiac pathology. We found that CHIKV infection induced IL-17A production in the heart, and that mice deficient in Il17a ( Il17a -/- ) and in its receptor gene, Il-17ra ( Il17ra -/- ), exhibited marked resistance to CHIKV infection in both cardiac tissue and primary cardiac fibroblasts. Genetic deletion of IL-17A signaling significantly enhanced type I interferon responses and decreased viral burden in mouse hearts. Interestingly, blockade of IL-17RA with an FDA-approved monoclonal antibody for plaque psoriasis, Brodalumab, drastically increased type I interferon production and reduced viral replication in both human cardiac fibroblasts and human embryonic kidney 293 (HEK 293) cells. In addition, inhibition of IL-17A signaling suppressed the expression of pro-inflammatory mediators, including Il-1β , Tnf-α , and Cxcl2 , reduced immune cell infiltration into cardiac tissue, and mitigated cardiac injury. Importantly, therapeutic blockade of IL-17A signaling after CHIKV infection reduced viral replication in both the heart and circulation. Collectively, these findings identify IL-17A signaling as a critical regulator of CHIKV replication and cardiac inflammation and highlight the IL-17A/IL-17RA axis as a promising therapeutic target for CHIKV-associated cardiovascular disease. Chikungunya virus (CHIKV) infection has been frequently associated with cardiovascular complications, yet the host pathways that promote viral infection and cardiac injury remain poorly understood. Here, we identify IL-17A signaling as a previously unrecognized regulator of CHIKV pathogenesis in the heart. Using a novel heterozygous interferon receptor-deficient mouse model and primary human cardiac fibroblasts, we demonstrate that IL-17A signaling facilitates CHIKV replication via suppressing antiviral type I interferon responses. Genetic deletion or pharmacological blockade with an FDA-approved monoclonal antibody of IL-17A signaling reduced viral burden, attenuated inflammatory cytokine production, limited immune cell infiltration, and protected against cardiac injury. Importantly, therapeutic inhibition of IL-17A signaling after infection remained effective in reducing viral replication in both cardiac tissue and circulation and mitigating cardiac damage. These findings reveal a critical role for the IL-17A/IL-17RA axis in linking antiviral immunity to CHIKV-induced cardiovascular disease and identify a potential translatable therapeutic target for CHIKV-caused cardiac complications.
2026-05-23 | CONVICTION-CHIK study on the effect of convalescent plasma for mother-to-child Chikungunya infection: protocol for a multicentre, open label, single-arm, phase II trial.
Mother-to-child peripartum transmission of Chikungunya infection may induce severe illness with neonatal encephalitis/encephalopathy, leading to major neurological sequalae in offspring. There is not, at present, any licensed vaccine or treatment for Chikungunya virus (CHIKV) disease in pregnant women or neonates. However, there are a range of potential treatments, including passive immune therapies by hyperimmune antibodies or blood products, which warrant further investigation. Our study aims to determine whether the early administration of CHIKV convalescent plasma donor is effective in preventing several adverse outcomes in neonates exposed to maternal peripartum CHIKV infection. CONVICTION-CHIK is a multicentre, interventional, phase II, single-arm trial, that will be conducted in two French overseas departments in the Indian Ocean throughout 2026. Neonates with the following criteria will be included: (1) mother with a clinical and/or biological diagnosis of CHIKV infection occurring between day -2 and + 2 around delivery; (2) cared for in a 3rd level neonatal intensive care unit; (3) treatment administration possible within 12 h from diagnosis of maternal infection. The intervention consists in the transfusion of 25 mL/kg of ABO CHIKV convalescent plasma over 4 h. The primary endpoint is the proportion of newborn infants treated with CHIKV convalescent plasma who survive without encephalitis/encephalopathy in the first 5 days of life. This outcome will also be assessed in a parallel cohort of untreated newborn infants exposed to peripartum CHIKV infection. Secondary endpoints are clinical, biological, and brain imaging findings of neonatal CHIKV infection, in treated and untreated neonates. Based on an expected decrease in the primary endpoint from 25% to 3% in the intervention group, the required sample size is 30 treated neonates. A parallel cohort of 30 contemporaneous untreated neonates will be enrolled to provide exploratory context for the observed treatment effect. If successful, this research will expand the therapeutic arsenal for treating peripartum neonatal CHIKV infection, in addition to symptomatic management of organ failure. The results of this study will allow to consider the feasibility to implement the systematic collection of convalescent plasma following Chikungunya outbreaks, for the management of subsequent epidemics. NCT07190560 (registered 17 September 2025).
2026-03-25 | E2 Protein of Chikungunya Virus: A Narrative Review of Its Potential as a Therapeutic Target.
Chikungunya Virus (CHIKV), an enveloped RNA virus transmitted by Aedes mosquitoes, has become an increasing global health concern, particularly in South America, where cases and fatalities have risen (PAHO, 2023). This review focuses on therapeutic strategies targeting the CHIKV E2 protein, including vaccines, antibodies, and antiviral approaches tested in vitro and in vivo. Literature reporting on the E2 protein, including studies on viral structure, host interactions, symptoms, and treatments under development, was analyzed. The E2 protein, a major structural component of CHIKV, is critical for viral entry and virulence, mediating interactions with host factors (Glycosaminoglycans (GAGs) and C-type lectins) and receptors (Matrix Remodeling-Associated Protein 8 (Mxra8) and Prohibitin-1 (PHB1)). It also elicits robust antibody responses, making it a key target for therapeutic intervention. The E2 protein is essential for CHIKV entry and virulence, making it a key target for vaccines, antibodies, and antivirals. While preclinical studies show promise, efficacy varies and clinical translation remains limited. Challenges include viral diversity, immune escape, and the need for integrated strategies combining different therapeutic approaches. Given the absence of licensed vaccines and antivirals for alphaviruses, the E2 protein represents a promising therapeutic target while inhibiting E2 could block viral entry and infection. However, current strategies show variable efficacy and inconclusive results, highlighting the need for further research to validate and optimize E2-targeted therapies.
2026-01-29 | Human autoantibodies against type I interferons in severe viral disease.
Type I interferons (IFN-Is) are critical antiviral cytokines that restrict viral replication and limit viral disease. A remarkable recent discovery is that human autoantibodies (autoAbs) neutralizing the activities of IFN-Is phenocopy inborn errors of immunity and markedly exacerbate susceptibility to life-threatening infections. Development of these pathogenic autoAbs in humans is strongly linked to genetic and nongenetic factors affecting thymic function, and they are estimated to be present in >100 million people worldwide with a prevalence that increases with age. Here, we review major advances from the last few years that have improved our mechanistic understanding of human IFN-I autoAb development and function, as well as their association with a significant proportion of different severe viral diseases. In particular, we highlight how neutralizing IFN-I autoAbs can persist in individuals for decades, compromising IFN-I-mediated defenses, and underlying subsequent critical infections with diverse pathogens, including SARS-CoV-2, West Nile virus, tick-borne encephalitis virus, seasonal influenza viruses, herpesviruses, and rare zoonoses caused by MERS-CoV, flaviviruses, and avian H5N1 influenza A virus. Furthermore, we discuss how neutralizing IFN-I autoAbs facilitate severe adverse events with live-attenuated viral vaccines, such as the yellow fever or chikungunya virus vaccines, and suggest how implementation of IFN-I autoAb diagnostics in at-risk populations may be clinically beneficial with current prophylactic or therapeutic options. Finally, in the context of new experimental insights into how autoAbs block the ability of IFN-Is to engage with the IFNAR1/IFNAR2 receptors, we detail future opportunities to design advanced novel therapeutic strategies that might specifically mitigate IFN-I autoAb pathogenic effects.
other
2026-09-26 | Chikungunya Virus E2 N218K Enhances Heparan Sulfate-Dependent Attachment and Viral Internalization While Conferring Partial Attenuation in A129 Mice.
The E2 glycoprotein of chikungunya virus (CHIKV) binds negatively charged cell-surface heparan sulfate (HS) to facilitate viral attachment and modulate pathogenicity, yet the E2 determinants governing HS-dependent attachment and the effects of altered HS utilization on subsequent infection remain incompletely defined. From a low-passage clinical isolate obtained during the 2010 Guangdong outbreak, we identified a previously unreported E2 substitution, N218K, which introduces a basic residue. In vitro, this mutation enhanced early infection and attachment to mammalian cells and reduced the RNA/PFU ratio; in A129 mice, however, it reduced early serum viral RNA levels, was associated with lower tissue viral RNA burdens at 5 dpi, and delayed mortality, consistent with partial attenuation. Soluble HS competition assays showed that N218K increased HS dependence during viral attachment, whereas DEAE-dextran assays supported a role for charge-dependent interactions in restricting local viral spread. N218K also enhanced viral internalization after normalization of initial attachment, identifying an additional post-attachment phenotype associated with this substitution. Our findings identify N218K as a determinant of HS-dependent attachment and partial attenuation in A129 mice, reveal a "high attachment-low dissemination" phenotype, and further show that this charge-altering E2 substitution enhances post-attachment internalization.
2026-09-14 | A Restriction-Free Cloning Approach for Molecular Engineering of Plasmids.
Molecular cloning by PCR amplification using a highly processive, high-fidelity DNA polymerase represents a robust and versatile technique for the precise manipulation of nucleic acid sequences. This approach enables the insertion, replacement, or modification of specific DNA fragments within a cloning vector, thereby generating an accurate copy of a gene or viral segment for downstream applications, such as protein expression, site-directed mutagenesis, and structural or functional analyses. The use of processive, high-fidelity polymerases significantly reduces the occurrence of base substitution errors, ensuring sequence integrity throughout the amplification process. Traditionally, restriction enzymes have been employed to facilitate directional cloning; however, alternative methods allow for mutagenesis without the need for unique and specific restriction sites and can be applied to virtually any cloning or seamless DNA assembly strategy. In this chapter, we describe a restriction enzyme-free and ligation-free PCR-based protocol widely applicable to any circular vector. This method enables targeted mutagenesis of the chikungunya virus (CHIKV) genome, offering a fast, efficient, and reliable strategy for generating mutant constructs suitable for virological and molecular studies.
2026-08-28 | Effects of different X-ray irradiation dosages on Wolbachia trans-infected and uninfected Aedes aegypti mosquitoes.
Aedes aegypti is a primary vector of several arboviral diseases, including dengue, chikungunya, Zika, and yellow fever. Eliminating Ae. aegypti can disrupt virus transmission cycles, thereby reducing the incidence of these diseases. Releasing sterile Ae. aegypti males has been implemented to suppress their natural populations, using three approaches, i.e., ionizing radiation-induced sterilization (Sterile Insect Technique, SIT), Wolbachia-induced cytoplasmic incompatibility (Incompatible Insect Technique, IIT), and a combination of both approaches (SIT/IIT). This study investigated effects of different X-ray radiation doses on the ecological fitness of the Thai wild-type and Wolbachia trans-infected Ae. aegypti. Both wild-type and wAlbB trans-infected Ae. aegypti were irradiated with different X-ray radiation dosages, i.e., 30, 50, and 70 Gy, at the pupal stage. Our results demonstrated reduced fitness parameters in both Ae. aegypti strains when irradiation dosages increased, with greater adverse effects observed in the Wolbachia-infected group. Interestingly, 30 Gy irradiation appeared to prolong the lifespan of wAlbB trans-infected Ae. aegypti. Male fertility in both wild-type and wAlbB trans-infected mosquitoes irradiated at 50 Gy and 70 Gy was nearly zero. Wolbachia density generally declined with increasing radiation, and higher doses were associated with reduced mating competitiveness. At 30 Gy, wild-type males outperformed wAlbB trans-infected males in mating competitiveness; but it was reversed at 50 Gy and 70 Gy. Based on the evaluation of ecological fitness parameters and mating competitiveness across various X-ray dosages under laboratory conditions, 30 Gy is recommended for sterilizing both Thai wild-type and wAlbB trans-infected Ae. aegypti. Our findings aim to improve the efficiency of sterile mosquito release programs, thereby suppressing Ae. aegypti vector populations and mitigating the risk of arboviral disease transmission.
2026-07-28 | Single-stranded nucleic acid binding enhances the in vitro catalytic activity of Chikungunya virus nsP2 protease.
Chikungunya virus (CHIKV) is an emerging arbovirus whose replication relies on the multifunctional nonstructural protein 2 (nsP2), particularly its viral protease (nsP2pro), which is essential for polyprotein processing. In this study, we investigated how interactions with nucleic acids influence nsP2pro activity. Using High-Throughput Sequencing-Fluorescent Ligand Interaction Profiling (HiTS-FLIP), we identified specific single-stranded DNA aptamers that enhanced nsP2pro activity. Additionally, both random single-stranded DNA and single-stranded RNA were found to stimulate protease activity, whereas double-stranded DNA showed no such effect. Circular dichroism spectroscopy and secondary structure predictions confirmed that the identified aptamers adopt stable folded conformations. Similarly, structured RNA sequences were also capable of promoting protease activity. The observed stimulatory effect depended on the nucleic acid strand type, length, and buffer conditions, suggesting the involvement of electrostatic interactions. NMR experiments demonstrated that nsP2pro interacts with single-stranded DNA, accompanied by changes in its conformational dynamics upon binding. Molecular dynamic simulations of nsP2pro-RNA and -DNA complexes revealed that these nucleic acids interact specifically with the nsP2pro methyltransferase domain and induce an opening process in the protease active site. Our findings provide novel insights into the regulation of nsP2pro, enhancing our understanding of CHIKV replication mechanisms, and may guide future antiviral development strategies.
2026-05-24 | Aptamers as immunomodulatory therapeutic alternatives targeting neglected tropical diseases (NTDs).
Neglected tropical diseases (NTDs) comprise a heterogeneous group of infections that disproportionately affect populations in low- and middle-income countries, where limited access to diagnostics, therapeutics, and surveillance perpetuates disease burden. Conventional strategies based on antibodies and small-molecule drugs face major challenges, including high production costs, limited stability, cross-reactivity, toxicity, and the emergence of drug resistance. In this context, aptamers, short single-stranded nucleic acids selected by SELEX, have emerged as versatile immunomodulatory tools with significant potential for the diagnosis and treatment of NTDs. This chapter provides a comprehensive overview of aptamer-based strategies targeting major NTDs, with particular emphasis on human African trypanosomiasis and arboviral infections such as dengue, Zika, and chikungunya. Aptamers directed against conserved parasite and viral epitopes demonstrate the capacity to circumvent immune evasion mechanisms, including antigenic variation and serotype diversity, while enabling highly specific recognition and internalization. In African trypanosomes, RNA aptamers targeting variant surface glycoproteins exploit the flagellar pocket for targeted drug delivery, offering a novel approach to overcome therapeutic resistance. In arboviral diseases, aptamers have been successfully integrated into advanced diagnostic platforms, including competitive ELISA, electrochemical, and capacitive biosensors, achieving high sensitivity, rapid response times, and minimal cross-reactivity among closely related flaviviruses. Beyond diagnostics, selected aptamers exhibit neutralizing activity and immunomodulatory effects by interfering with host-pathogen interactions and innate immune signaling pathways.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.