RARE DISEASE
Ebola hemorrhagic fever
Ebola hemorrhagic fever
Ebola hemorrhagic fever
Synonyms: EHF, Ebola fever, Ebola virus disease
Synonyms: EHF, Ebola fever, Ebola virus disease
Synonyms: EHF, Ebola fever, Ebola virus disease
Drug discovery
22
drugs
With orphan designations
Overview
Ebola hemorrhagic fever (EHF), caused by Orthoebolavirus species, is a severe viral illness characterized by abrupt fever, myalgia, and gastrointestinal symptoms, progressing to hemorrhagic manifestations, multi-organ failure, and shock. Case fatality ranges from 50% to 90%, depending on the viral species and healthcare access [2][9][17]. Transmission occurs via direct contact with infected body fluids, with outbreaks primarily in sub-Saharan Africa. Diagnosis relies on PCR detection, while treatment combines monoclonal antibodies (REGN-EB3, mAb114) for Ebola Zaire and aggressive supportive care [1][8][10][20].
Therapies
Monoclonal antibodies: REGN-EB3 and mAb114 (FDA-approved for Zaire ebolavirus), reducing mortality when administered early [8][10][16].
Supportive care: IV fluids, electrolyte replacement, and management of sepsis/septic shock [5][16][20].
Investigational agents: Oral antivirals (e.g., obeldesivir) show promise in preclinical trials [13].
Categories: rare infectious diseases
Research Papers
2,120 drug discovery papers about Ebola hemorrhagic fever, with 3 first-in-class and 19 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,120 drug discovery papers about Ebola hemorrhagic fever, with 3 first-in-class and 19 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
antibodies
2026-09-15 | From Group Intervention to Precision Strike: Insights from Ebola Virus for Future Infectious Disease Management
The 2014–2016 West African Ebola outbreak exposed systemic deficiencies in traditional public health approaches to managing highly lethal infectious diseases, while also marking a transformative turning point for breakthroughs in precision medicine technologies. This study systematically examines the Ebola virus, analyzing its transmission scale and historical challenges in containment. By comparing the effectiveness of traditional medical interventions with rapid diagnostics and targeted therapies, this paper highlights the critical role of precision medicine in infectious disease prevention and control. Research findings demonstrate that CRISPR-based on-site detection significantly reduces diagnostic time, monoclonal antibody drugs (e.g., REGN-EB3) lower mortality rates from 49% to 29%, and multi-omics-driven host-pathogen interaction analyses provide novel pathways for high-risk population screening and personalized vaccine design. Further exploration reveals that precision medicine is shifting infectious disease management from "passive response" to "precision intervention." Finally, article proposes that future infectious disease prevention and control can establish a "prediction-warning-precision intervention" trinity framework, with the expectation of providing reference and basis for subsequent related research.
2026-09-15 | Post-Exposure Prophylaxis with a monoclonal antibody cocktail Following Bundibugyo Ebolavirus Exposure in Adults and Children.
Five individuals from a single-family cluster, one rVSV-ZEBOV-vaccinated adult and four unvaccinated children aged 1-7 years, received investigational MBP134 as post-exposure prophylaxis (PEP) 5-6 days after high- to intermediate-risk occupational or household exposure to Bundibugyo ebolavirus (BDBV). MBP134 is a broadly neutralizing monoclonal antibody cocktail that has conferred protection against BDBV in non-human primates but to our knowledge has not previously been evaluated as PEP in humans. Given the absence of approved preventive interventions against BDBV and the substantial case fatality rate of Bundibugyo virus disease (BVD), MBP134 was administered as an individual treatment attempt under emergency Investigational New Drug (eIND) authorizations. Administration was well tolerated, with no treatment-related adverse events. Throughout the 21-day monitoring period, all family members remained free of clinical or laboratory evidence of BVD, as assessed by daily medical evaluation and serial PCR testing. Plasma Orthoebolavirus-reactive antibodies were detected after infusion, persisted throughout follow-up and mediated broad neutralizing activity against multiple Orthoebolavirus species, including authentic BDBV. Notably, endogenous BDBV-reactive IgM and IgA were detected in the adult following high-risk exposure despite persistently negative PCR results. Together, these findings support prospective evaluation of MBP134 as PEP for high-risk adult and pediatric contacts during BDBV outbreaks.
2026-09-01 | How mistrust emerged in real time in the Bundibugyo virus disease outbreak: ‘Ebola business’, social media and the history of mistrust in Ebola epidemics in eastern Congo
On 15 May 2026, Congolese health authorities declared a Bundibugyo virus disease (BVD) outbreak in Mongbwalu and Bunia in Ituri Province. BVD is caused by the Bundibugyo virus, one of four orthoebolavirus species that cause Ebola disease in humans. This species is much rarer than Zaire ebolavirus, which has caused most previous Ebola virus disease (EVD) outbreaks. In the months since its declaration, the outbreak has become one of the swiftest on record. 1 The pace of this outbreak raises an old question with new urgency: how could the medical humanitarian apparatus of Ebola response be caught, once again, unprepared?2 Delayed declaration of this outbreak and the absence of proven treatments and vaccines3 are certainly part of the answer.1
2026-08-28 | A novel Fc-optimized anti-Ebola neutralizing antibody with extended in vivo half-life.
Zaire Ebola virus (EBOV) is one of the main pathogens causing Ebola hemorrhagic fever. The whole human monoclonal antibody Mab114, which can specifically recognize EBOV, has good functions of neutralizing the virus and improving the survival rate of infected animals. The longer in vivo half-life of antibody drugs is mainly achieved through pH dependent binding of the receptor FcRn. This study used computer simulation methods to construct the spatial conformation of human Fc and human FcRn complexes based on molecular docking and mechanical optimization. The key structural domains and important amino acid sites for the binding of human Fc and human FcRn were determined. Based on this, two Fc mutants were designed, and two Fc mutant antibodies Mab114-M5 and Mab114-M6 were constructed using whole human monoclonal antibody Mab114 as the model antibody. The affinity, in vivo and in vitro neutralization function, in vivo serum metabolism of human FcRn transgenic mice, and in vivo antiviral activity were verified through experiments. The results showed that the mutant antibody had a significantly longer retention time in mice compared to Mab114, and also exhibited similar activity in neutralizing EBOV as the maternal antibody Mab114. Fc mutants have the potential to have a long half-life in vivo, thereby reducing medication frequency and providing new ideas for the development of long-acting antibody therapy drugs.
2026-08-19 | A Review of the Current Status of Antiviral Drugs Targeting Human Immunodeficiency Virus, Hepatitis and Others.
Antiviral drugs are pivotal in the prevention and management of infections caused by viruses, ranging from common cold viruses to life-threatening pathogens like human immunodeficiency virus, hepatitis viruses, Ebola virus, etc. Furthermore, antiviral therapy is increasingly being integrated into the management of chronic viral infections to restrain their replication, avert disease progression, and minimize the risk of complications. The availability of newer generations of antiviral drugs, particularly direct-acting antivirals, and combination therapies have significantly improved treatment outcomes, offering better cure speed, shorter treatment time, and reduced side effects as compared to older-generation antivirals. This comprehensive review provides an in-depth analysis of the diverse classes of antiviral drugs, their mechanisms of action, clinical applications, challenges, and future directions. With a focus on recent advancements and emerging trends, the current landscape of antiviral drug development and its implications for global public health are also discussed.
vaccines
2026-09-21 | Systemic and Mucosal Immune Responses From Serotype-Switched Viral-Vectored Ebola Vaccines.
Ebola virus is a highly virulent pathogen causing severe hemorrhagic fever with 25%-90% mortality. The 2014 outbreak infected over 28,000 people, causing 11,325 deaths. Although there is one FDA-approved vaccine available for limited use, additional vaccines are needed. We developed adenoviral-vectored vaccines expressing the ebolavirus glycoprotein (GP), the sole viral surface protein and primary immunogen. Vaccine constructs spanned three species and five human adenovirus subtypes, including low-seroprevalent serotypes to minimize pre-existing immunity. We compared single-dose and prime-boost regimens, intramuscular versus needle-free intranasal delivery, and serotype-switching strategies. Immunogenicity was assessed by quantifying GP-specific antibodies and T cell responses in BALB/c mice. Species C vectors (Ad5 and Ad6) elicited strong antibody responses and promoted rapid class switching to IgG compared to species B and D vectors. Serotype-switched regimens further enhanced antibody levels via intramuscular or intranasal routes and generated robust T cell responses when delivered intramuscularly. Intranasal vaccination induced detectable IgA but no measurable T cell responses, indicating route-dependent immune compartmentalization. Sera partially inhibited viral entry in a dose-dependent manner, with the greatest reduction observed in the Ad5/Ad6 regimen. Collectively, adenoviral species selection, serotype switching, and route of administration significantly influence GP-specific immunity and warrant further evaluation in protective challenge models.
2026-09-07 | Pan-Ebolavirus nanoparticle vaccine provides protection in rodents from lethal infection by Zaire and Sudan viruses.
Both Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) are members of the genus Ebolavirus and cause outbreaks marked by high fatality rates and repeated spillover from animal reservoirs. Filoviral glycoproteins (GPs) are the primary targets of neutralizing antibodies and form the basis of current vaccines. Here we describe the design, structural characterization, and evaluation of two-component self-assembling icosahedral I53-50 nanoparticles displaying prefusion EBOV or SUDV GP antigens, either individually or in cocktail and mosaic multivalent formats. EBOV-GP-I53-50 and SUDV-GP-I53-50 nanoparticles elicited strong homologous protection in mice and guinea pigs. In the mouse-adapted EBOV model (maEBOV), mosaic and cocktail formulations produced weak survival below that of the matched EBOV-GP-I53-50 GP immunogen. In contrast, in the gpaSUDV guinea pig model (gpSUDV), cocktail and mosaic nanoparticles elicited robust protection against gpSUDV, and detectable antibody responses to both SUDV and EBOV GPs. These findings demonstrate that multivalent GP-I53-50 nanoparticle immunogens can protect rodents from death, severe clinical signs of disease, and weight loss in relevant models. Together with the established clinical safety of the I53-50 platform, these results support continued efforts toward the development of a pan-ebolavirus vaccine.
2026-08-13 | 'Mismatched' Ebola vaccine may soon be rolled out widely.
Opinions shift after new data suggest vaccine for Ebola Zaire may also protect against Bundibugyo.
2026-06-05 | Cross-reactive Bundibugyo antibody responses after licensed Ebola vaccines.
The ongoing Bundibugyo virus disease (BDBV) outbreak in Central Africa highlights the absence of approved vaccines specifically targeting BDBV. Whether licensed Zaire ebolavirus (EBOV) vaccines induce cross-reactive immunity against BDBV remains largely unknown. We performed an immunogenicity analysis using serum samples from participants enrolled in the PREVAC randomized clinical trial evaluating licensed Ebola vaccine strategies in West Africa. Samples collected at day 28 (D28) and month 3 (M3) following vaccination with rVSVΔG-ZEBOV-GP or Ad26.ZEBOV/MVA-BN-Filo were assessed using a multiplex Luminex assay against glycoproteins from multiple filoviruses, including EBOV Kikwit, EBOV Mayinga, BDBV, Sudan virus, Reston virus, and Marburg virus. A total of 179 samples were analysed. Detectable cross-reactive antibody responses against BDBV were observed across vaccine groups, timepoints, and age categories. However, BDBV responses remained substantially lower than homologous EBOV responses. In rVSV recipients, median BDBV responses (net MFI) reached 282 (IQR 164-644) at D28 compared with 1788 (832-3311) against the homologous Kikwit antigen. Similar patterns were observed following rVSV booster vaccination and Ad26.ZEBOV/MVA-BN-Filo vaccination. The heterologous Ad26/MVA regimen demonstrated increasing BDBV responses between D28 and M3. Licensed EBOV vaccines induced detectable but quantitatively reduced cross-reactive antibody responses against BDBV. Although no direct assessment of vaccine efficacy against BDBV disease was possible, these findings support the plausibility of partial heterologous immunity following EBOV vaccination. In the absence of approved BDBV-specific vaccines, these data support the urgent evaluation of currently available Ebola vaccines during BDBV outbreaks and reinforce the importance of developing broadly protective pan-filovirus vaccines.
2026-06-04 | Pan-pathogen vaccine approaches: Toward broad-spectrum immunity in a One Health era.
Emerging and re-emerging infectious diseases (EIDs) represent an escalating threat to global public health, as exemplified by outbreaks of COVID-19, Ebola, Zika, and other zoonotic viruses. Traditional pathogen-specific vaccines, although effective for individual diseases, face significant limitations in addressing EIDs due to long development timelines, resource intensity, and restricted adaptability to novel pathogens or variants. Pan-pathogen vaccines-designed to provide broad-spectrum immunity across multiple related or unrelated pathogens-offer a transformative approach to pandemic preparedness. This review presents a comprehensive overview of pan-pathogen vaccinology within the One Health framework, emphasizing the integration of human, animal, and environmental health for proactive disease prevention. We provide explicit definitions for "universal", "broad-spectrum", and "pan-pathogen" vaccines and embed the One Health principle into the full vaccine development lifecycle through real-world case studies, including Nipah virus and rVSV-Ebola. The review highlights strategies for epitope discovery using comparative genomics, evolutionary biology, and immunoinformatics to identify conserved antigenic regions, and details mechanisms of cross-protective immunity mediated by T cells, broadly neutralizing antibodies, mucosal responses, and trained innate immunity with emphasis on their interplay. Advanced vaccine platforms-mRNA, viral vectors, protein subunits, and nanoparticle-based systems-are evaluated for their capacity to deliver multivalent, chimeric, and mosaic antigens. Preclinical and clinical advances against influenza, coronaviruses, flaviviruses, filoviruses, and critically, bacterial, fungal, parasitic, and DNA virus targets are summarized. Ethical, regulatory, and global health considerations for equitable vaccine distribution are discussed, with expanded safety analysis addressing pan-pathogen-specific hazards such as antigenic competition, autoimmunity, and regulatory adaptation. Persistent gaps, including antigenic variability, immune imprinting, safety concerns, and challenges in clinical validation, are identified, alongside controversies surrounding the balance between broad coverage and potential immune escape. Integrating genomic surveillance, predictive modeling, and emerging technologies such as artificial intelligence, systems biology, and synthetic vaccinology is essential to optimize vaccine design and accelerate translational implementation. Collectively, pan-pathogen vaccines represent a proactive, adaptive, and globally coordinated strategy to mitigate future pandemics and strengthen long-term health security.
small molecules
2026-09-23 | An expanded hypothesis: The role of ascorbate and glucose in the intracellular processes and immunobiology of Ebola virus haemorrhagic fever
The opposing effects of glucose and ascorbate transport on physiological processes may help explain Ebola virus disease pathophysiology. The virus impairs intracellular interferon (IFN) signalling. High plasma glucose levels contribute to oxidative stress and may also inhibit IFN signalling. Conversely, ascorbate may counteract the virus-mediated IFN blockade and interfere with viral budding. Dysregulation of glucose and ascorbate homeostasis may contribute to the pathophysiology of Ebola virus haemorrhagic fever by promoting oxidative stress, activation of the nuclear factor kappa B (NF-κB) pathway, and a cytokine storm. Hyperglycaemia commonly occurs in critically ill patients with Ebola virus haemorrhagic fever. Therefore, haemorrhagic fever syndrome could be understood as a state of oxidative stress driven by hyperglycaemia, NF-κB pathway activation, and inflammatory cytokines. A potential treatment strategy would focus on administering ascorbate and glutathione, together with glucose or insulin as appropriate, to maintain normal, stable plasma glucose levels and combat oxidative and inflammatory stress.
2026-07-28 | PTPN13 Contributes to Ebola Virus-Induced Immune Dysregulation via Dephosphorylation of IRF3 and PI3K-p85.
Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-β while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFNβ and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFNβ and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85.
2026-07-17 | AI-Driven Discovery and BSL-4 Validation of Cross-Filovirus Ebola-Marburg Inhibitors and their Synergistic Combinations.
Filovirus outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV), pose severe global health threats characterized by high rates of fatal hemorrhagic fever. While species-specific vaccines and therapeutic monoclonal antibodies are approved for Zaire ebolavirus, broadly-active therapeutics remain unavailable, leaving populations vulnerable to MARV and other pathogenic Ebola species, such as Bundibugyo (BDBV) and Sudan (SUDV) ebolaviruses. Here we report a computationally guided, infectious virus validated screening platform for the rapid discovery of broad-spectrum filovirus antivirals. By leveraging quantitative structure- activity relationship (QSAR) models, we screened 142,382 compounds in silico to prioritize 125 high-potential candidates. Subsequent dose-response and viability profiling identified 23 compounds exhibiting potent, low-micromolar pan-filovirus activity and favorable cytotoxicity profiles. Molecular docking indicates these compounds target conserved structural and functional domains-primarily the VP35 and L proteins-which may disrupt essential viral replication and immune antagonism. Furthermore, systematic combinatorial screening revealed three highly synergistic compound pairs, notably NCGC00113249-01 and NCGC00118008-01, demonstrating robust cross-species efficacy. By targeting conserved vulnerabilities across the filovirus family, this integrated in silico and in vitro pipeline provides a scalable framework to rapidly nominate and optimize synergistic therapeutic regimens against both endemic and emerging viral threats including BDBV.
2026-06-28 | A New Proposal for Host-Directed Therapy in Ebola Virus Disease: Ozone Autohemotherapy as an Adjunctive Approach Within a Systems Biology Framework
Ebola Virus Disease (EVD) remains one of the most lethal viral hemorrhagic fevers, with mortality driven not only by viral replication but also by a dysregulated host response characterized by hyperinflammation, endothelial dysfunction, coagulopathy, metabolic derangement and multi-organ failure. Although monoclonal antibodies and vaccination have substantially improved outcomes, currently available interventions primarily target the virus and do not directly address the complex host-response networks that contribute to advanced disease and mortality. Here, we propose a systems biology framework for evaluating Ozone Autohemotherapy (O₃-AHT), specifically Major Autohemotherapy (MAH), as a host-directed adjunctive strategy in EVD. The framework is based on the capacity of O₃-AHT to generate controlled redox signals through Reactive Oxygen Species (ROS) and Lipid Ozonation Products (LOPs), which activate adaptive stress-response pathways including the Nrf2/Keap1/Antioxidant Response Element (ARE) system, the AMP-Activated Protein Kinase (AMPK)-Forkhead Box O (FOXO)-mechanistic Target of Rapamycin (mTOR)-sirtuin 1 (Sirt1) axis and Nrf2-mediated modulation of Nuclear Factor Kappa B (NF-κB) signaling. These interconnected pathways regulate antioxidant defenses, mitochondrial adaptation, autophagy, inflammatory responses, endothelial homeostasis and immune regulation-biological processes that intersect with major pathogenic mechanisms of EVD. Particular attention is given to Heme Oxygenase-1 (HO-1), a downstream effector of Nrf2 activation for which experimental evidence demonstrates suppression of Ebola virus replication in-vitro, providing a mechanistic bridge between host-directed redox modulation and antiviral activity. By integrating current knowledge from virology, immunology, redox biology and systems medicine, this framework identifies multiple points of convergence between ozone-induced adaptive signaling and Ebola pathophysiology. This work does not establish clinical efficacy but presents a hypothesis-generating model intended to guide future experimental investigation. As a conceptual framework, it proposes O₃-AHT as a candidate host-directed adjunctive approach that warrants systematic evaluation in preclinical models of Ebola virus disease.
2026-06-17 | Molecular phenotypes of sex and age specific differences relating to outcome in patients with Ebola virus disease.
Ebola virus (EBOV) causes a severe, potentially fatal, disease, with outcome likely related to both viral and host factors. There is a clear correlation between viral load and outcome (survival/death) and inflammatory as well as other cellular pathways are differentially activated in the acute stage between patients who go on to survive versus those who go on to die. Age and sex may influence the course of Ebola virus disease (EVD) with potential differences at the molecular level. To investigate whether there were age and/or sex-specific differences in patients with EVD, previously published data from an RNAseq analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak was stratified according to age/sex of the individual. This was correlated with the outcome of infection. Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalised survivors compared to hospitalized fatal cases, regardless of the sex of the patient. However, aspects of the blood transcriptome/host response differed between females and males and certain age groups at the transcriptomic level. Genes associated with the lymphocyte differentiation pathway decreased in expression level with age in hospitalised fatal cases. However, this was the opposite in hospitalised survivors. From a medical countermeasure perspective, the work indicated that selection of animal models should consider age and sex, depending on the research question, and cellular pathways were identified that could be chemotherapeutically enhanced to promote survival.
proteins
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-06-25 | Development of Peptide Entry Inhibitors Targeting the Endosomal Receptor NPC1 Binding Site of Orthoebolavirus.
Orthoebolavirus causes severe Ebola virus disease (EVD) and deadly outbreaks in humans. This infection occurs through macropinocytosis and trafficking to late endosomes or lysosomes that utilize the receptor Niemann-Pick C1 (NPC1) to enter the cell cytoplasm. We designed peptide inhibitors based on the NPC1 receptor to target the NPC1 binding site to block viral entry. The results indicated that the ligand-based peptide inhibitors showed potent inhibition activities in vitro studies against pseudotyped or replication-competent Orthoebolavirus. Therefore, we further evaluated one of them in a mouse model challenged with mice-adapted Ebola viruses, which showed some protection efficacy compared with the control group. This study suggests that ligand-based peptides are encouraging inhibitors in the development of inhibitors against Ebola virus infection.
2026-05-18 | Multivalent mRNA vaccine platform with compatible antigens conferred broad-spectrum protection against orthoebolaviruses' exposure.
Several orthoebolaviruses have been established, including Orthoebolavirus zairense [for Ebola virus (EBOV)], Orthoebolavirus sudanense [for Sudan virus (SUDV)], and Orthoebolavirus bundibugyoense [for Bundibugyo virus (BDBV)]. Orthoebolaviruses are highly virulent pathogens that cause severe disease in humans. However, most existing vaccines primarily target EBOV, and fail to provide robust cross-protection against other lethal orthoebolaviruses. The development of a broad-spectrum vaccine has the potential to efficiently mitigate outbreaks caused by multiple orthoebolaviruses. In this study, we developed and evaluated a broad-spectrum mRNA vaccine, designated [GPs+NP]@LNP, formulated with a single lipid nanoparticle (LNP) platform to encapsulate a mixed mRNA payload encoding the glycoproteins (GPs) of EBOV, BDBV, and SUDV, along with the nucleoprotein (NP) of EBOV. This rational antigenic combination was designed to engage both humoral and cellular arms of the immune system. Consistent with this design, the compatibility of humoral immunity-driving GPs and cellular immune-dominating NPs supports complementary immune responses, which together are associated with broad and durable protection against EBOV, BDBV, and SUDV in animal models. Antigenic coordination within a single LNP formulation may therefore represent an effective strategy to optimize vaccine immunogenicity, protective effect, durability, and safety. Collectively, these findings highlight [GPs+NP]@LNP as a promising approach for the development of next-generation vaccines targeting multiple pathogenic orthoebolaviruses.
2026-04-27 | Griffithsin-mediated inhibition of cellular entry of hemorrhagic fever viruses and insights into its mechanisms.
Griffithsin (GRFT), a lectin derived from the red algae Griffithsia, is known as an antiviral agent that binds to high-mannose glycans on viral envelope glycoproteins (GPs). In this study, we evaluated the antiviral activity of GRFT against Ebola virus (EBOV), Marburg virus (MARV), Lassa virus (LASV), Lujo virus (LUJV), and Crimean-Congo hemorrhagic fever virus (CCHFV), all of which cause severe and often fatal hemorrhagic fevers in humans. GRFT effectively blocked the entry of these viruses into cells, with stronger inhibition observed against LASV, LUJV, and CCHFV than against EBOV and MARV. This inhibitory effect depended on the lectin activity of GRFT, as its mutant lacking glycan-binding function completely lost the ability to inhibit the entry of these viruses into cells. We found that GRFT induced aggregation of virus-like particles (VLPs) derived from EBOV and MARV, whereas this activity was not observed with LASV- and LUJV-derived VLPs. Most of the escape mutants of LASV and LUJV GPs exhibited amino acid substitutions that likely disrupted GRFT binding by removing glycosylation sites at positions 79 and 73, respectively. Interestingly, other substitutions close to these positions, although unrelated to glycosylation, also contributed to reduced inhibitory activity of GRFT, suggesting a unique recognition mode in which both sugar chains and adjacent amino acid residues constitute the binding site structure for GRFT. Overall, our results provide insights into mechanisms underlying the antiviral effects of GRFT and highlight lectin-related activities as a key feature for broad-spectrum antiviral agents targeting highly glycosylated envelope GPs. Emerging and re-emerging infectious diseases, including viral hemorrhagic fevers, pose a major global health threat due to their potential for widespread outbreaks. Currently, treatment options for such diseases are limited and often ineffective against newly emerging viruses. Here, we demonstrate that Griffithsin (GRFT), a naturally derived lectin from red algae, inhibits the entry of multiple hemorrhagic fever viruses into host cells. By blocking key processes of the viral entry mediated by envelope glycoproteins, lectins such as GRFT can exhibit broad antiviral activity that could potentially overcome the limitations of existing treatments against emerging viruses. Our findings emphasize that targeting sugar chains and adjacent structures on viral glycoproteins with GRFT could provide a therapeutic strategy against diverse viral species. Such an approach is particularly valuable for newly emerging viruses for which specific countermeasures have not yet been established.
2026-03-12 | Development of VP30-targeted nanoparticles using DPS4 fusion peptides for the inhibition of Ebola virus.
Multiple outbreaks of Ebola virus in West Africa have posed significant threats to global public health owing to its high pathogenicity and fatality rates. Current treatments for Ebola Virus Disease are limited, underscoring the imperative for novel antiviral therapies. VP30, a critical RNA synthesis factor, interacts with nucleoprotein (NP) to facilitate Ebola viral genome transcription and replication. Notably, the host ubiquitin-ligase retinoblastoma-binding protein 6 (RBBP6) binds to VP30 at the same interface as NP, thereby inhibiting VP30-NP interactions and indicating that targeting this interface could advance antiviral drug development. In this study, we engineered six peptide mutants through amino acid substitutions at key VP30 binding sites. These mutants were fused to DNA-binding protein from starved cells 4 (DPS4) to assemble nanoparticles, enabling surface display of the peptides. Antiviral effects were evaluated using minigenome and transcription and replication-competent virus-like particles (trVLPs) systems. Among the variants, RPL1 and NPL3 peptides exhibited relatively strong apparent affinities with the VP30 and potent antiviral activity by disrupting Ebola viral genome transcription and replication. To elucidate the binding details between the peptides and VP30, we determined crystal structures of complexes between RPL1 or NPL3 peptides and VP30 via X-ray crystallography. Concurrently, molecular dynamics (MD) simulations revealed the dynamic binding processes of these peptides to VP30. Structural analyses confirmed that the peptides bind to the VP30/NP interface and compete with NP. Our findings demonstrate that DPS4-fusion peptides effectively deliver peptides into cells as nanoparticles and inhibit VP30-NP interactions, presenting a novel antiviral strategy for Ebola virus.
other
2026-07-17 | Ebola virus exploits host lncRNA LINC01740 to enhance ATF3 and suppress antiviral immune responses.
Ebola virus (EBOV) infection causes severe hemorrhagic fever marked by dysregulated cytokine production, impaired antiviral defenses, and multi-organ failure. Macrophages are primary targets of EBOV, and viral replication profoundly alters macrophage transcriptional programs, driving hyperinflammation. Although long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of immunity and viral pathogenesis, their roles in EBOV infection remain poorly understood. We performed comprehensive transcriptomic profiling of primary human monocyte-derived macrophages infected with the highly pathogenic EBOV Mayinga variant. Infection triggered extensive remodeling of both coding and non-coding transcriptomes, including hundreds of differentially expressed lncRNAs. Functional analysis of neighboring protein-coding genes of EBOV-induced lncRNAs (EVILs) revealed enrichment of pathways linked to cytokine signaling, transcriptional regulation, and cell signaling, all of which are central to Ebola virus disease (EVD) pathogenesis. Among the most strongly induced EVILs, LINC01740 and its neighboring protein-coding gene, Activating Transcription Factor 3 (ATF3), were significantly upregulated. Antisense oligonucleotide-mediated inhibition of LINC01740 reduced ATF3 mRNA and protein levels. CRISPR/Cas13d-mediated knockdown of ATF3 restored type I interferon (IFN-I) signaling and antiviral gene expression in EBOV-infected macrophages. Mechanistically, ATF3 functions as a negative regulator of IFN-I and type I interferon-stimulated gene expression, thereby suppressing antiviral immune responses in EBOV-infected macrophages. Together, these findings identify a previously unrecognized LINC01740-ATF3-IFN-I regulatory axis that EBOV exploits to promote immune suppression and viral replication.
2026-04-02 | leucine rich alpha-2-glycoprotein 1 (LRG1) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [68, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥ 0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [88, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [68, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of LRG1, some of which might be known to exist via wet labexperiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-12-23 | retinol dehydrogenase 13 (all-trans/9-cis) (RDH13) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [21, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [9, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [21, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of RDH13, some of which might be known to exist via wet lab experiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-11-28 | aldolase, fructose-bisphosphate A (ALDOA) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [65, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [20, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [65, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of ALDOA, some of which might be known to exist via wet lab experiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-07-10 | Data Sheet 1_Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo.pdf
The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies.
antibodies
2026-09-15 | From Group Intervention to Precision Strike: Insights from Ebola Virus for Future Infectious Disease Management
The 2014–2016 West African Ebola outbreak exposed systemic deficiencies in traditional public health approaches to managing highly lethal infectious diseases, while also marking a transformative turning point for breakthroughs in precision medicine technologies. This study systematically examines the Ebola virus, analyzing its transmission scale and historical challenges in containment. By comparing the effectiveness of traditional medical interventions with rapid diagnostics and targeted therapies, this paper highlights the critical role of precision medicine in infectious disease prevention and control. Research findings demonstrate that CRISPR-based on-site detection significantly reduces diagnostic time, monoclonal antibody drugs (e.g., REGN-EB3) lower mortality rates from 49% to 29%, and multi-omics-driven host-pathogen interaction analyses provide novel pathways for high-risk population screening and personalized vaccine design. Further exploration reveals that precision medicine is shifting infectious disease management from "passive response" to "precision intervention." Finally, article proposes that future infectious disease prevention and control can establish a "prediction-warning-precision intervention" trinity framework, with the expectation of providing reference and basis for subsequent related research.
2026-09-15 | Post-Exposure Prophylaxis with a monoclonal antibody cocktail Following Bundibugyo Ebolavirus Exposure in Adults and Children.
Five individuals from a single-family cluster, one rVSV-ZEBOV-vaccinated adult and four unvaccinated children aged 1-7 years, received investigational MBP134 as post-exposure prophylaxis (PEP) 5-6 days after high- to intermediate-risk occupational or household exposure to Bundibugyo ebolavirus (BDBV). MBP134 is a broadly neutralizing monoclonal antibody cocktail that has conferred protection against BDBV in non-human primates but to our knowledge has not previously been evaluated as PEP in humans. Given the absence of approved preventive interventions against BDBV and the substantial case fatality rate of Bundibugyo virus disease (BVD), MBP134 was administered as an individual treatment attempt under emergency Investigational New Drug (eIND) authorizations. Administration was well tolerated, with no treatment-related adverse events. Throughout the 21-day monitoring period, all family members remained free of clinical or laboratory evidence of BVD, as assessed by daily medical evaluation and serial PCR testing. Plasma Orthoebolavirus-reactive antibodies were detected after infusion, persisted throughout follow-up and mediated broad neutralizing activity against multiple Orthoebolavirus species, including authentic BDBV. Notably, endogenous BDBV-reactive IgM and IgA were detected in the adult following high-risk exposure despite persistently negative PCR results. Together, these findings support prospective evaluation of MBP134 as PEP for high-risk adult and pediatric contacts during BDBV outbreaks.
2026-09-01 | How mistrust emerged in real time in the Bundibugyo virus disease outbreak: ‘Ebola business’, social media and the history of mistrust in Ebola epidemics in eastern Congo
On 15 May 2026, Congolese health authorities declared a Bundibugyo virus disease (BVD) outbreak in Mongbwalu and Bunia in Ituri Province. BVD is caused by the Bundibugyo virus, one of four orthoebolavirus species that cause Ebola disease in humans. This species is much rarer than Zaire ebolavirus, which has caused most previous Ebola virus disease (EVD) outbreaks. In the months since its declaration, the outbreak has become one of the swiftest on record. 1 The pace of this outbreak raises an old question with new urgency: how could the medical humanitarian apparatus of Ebola response be caught, once again, unprepared?2 Delayed declaration of this outbreak and the absence of proven treatments and vaccines3 are certainly part of the answer.1
2026-08-28 | A novel Fc-optimized anti-Ebola neutralizing antibody with extended in vivo half-life.
Zaire Ebola virus (EBOV) is one of the main pathogens causing Ebola hemorrhagic fever. The whole human monoclonal antibody Mab114, which can specifically recognize EBOV, has good functions of neutralizing the virus and improving the survival rate of infected animals. The longer in vivo half-life of antibody drugs is mainly achieved through pH dependent binding of the receptor FcRn. This study used computer simulation methods to construct the spatial conformation of human Fc and human FcRn complexes based on molecular docking and mechanical optimization. The key structural domains and important amino acid sites for the binding of human Fc and human FcRn were determined. Based on this, two Fc mutants were designed, and two Fc mutant antibodies Mab114-M5 and Mab114-M6 were constructed using whole human monoclonal antibody Mab114 as the model antibody. The affinity, in vivo and in vitro neutralization function, in vivo serum metabolism of human FcRn transgenic mice, and in vivo antiviral activity were verified through experiments. The results showed that the mutant antibody had a significantly longer retention time in mice compared to Mab114, and also exhibited similar activity in neutralizing EBOV as the maternal antibody Mab114. Fc mutants have the potential to have a long half-life in vivo, thereby reducing medication frequency and providing new ideas for the development of long-acting antibody therapy drugs.
2026-08-19 | A Review of the Current Status of Antiviral Drugs Targeting Human Immunodeficiency Virus, Hepatitis and Others.
Antiviral drugs are pivotal in the prevention and management of infections caused by viruses, ranging from common cold viruses to life-threatening pathogens like human immunodeficiency virus, hepatitis viruses, Ebola virus, etc. Furthermore, antiviral therapy is increasingly being integrated into the management of chronic viral infections to restrain their replication, avert disease progression, and minimize the risk of complications. The availability of newer generations of antiviral drugs, particularly direct-acting antivirals, and combination therapies have significantly improved treatment outcomes, offering better cure speed, shorter treatment time, and reduced side effects as compared to older-generation antivirals. This comprehensive review provides an in-depth analysis of the diverse classes of antiviral drugs, their mechanisms of action, clinical applications, challenges, and future directions. With a focus on recent advancements and emerging trends, the current landscape of antiviral drug development and its implications for global public health are also discussed.
vaccines
2026-09-21 | Systemic and Mucosal Immune Responses From Serotype-Switched Viral-Vectored Ebola Vaccines.
Ebola virus is a highly virulent pathogen causing severe hemorrhagic fever with 25%-90% mortality. The 2014 outbreak infected over 28,000 people, causing 11,325 deaths. Although there is one FDA-approved vaccine available for limited use, additional vaccines are needed. We developed adenoviral-vectored vaccines expressing the ebolavirus glycoprotein (GP), the sole viral surface protein and primary immunogen. Vaccine constructs spanned three species and five human adenovirus subtypes, including low-seroprevalent serotypes to minimize pre-existing immunity. We compared single-dose and prime-boost regimens, intramuscular versus needle-free intranasal delivery, and serotype-switching strategies. Immunogenicity was assessed by quantifying GP-specific antibodies and T cell responses in BALB/c mice. Species C vectors (Ad5 and Ad6) elicited strong antibody responses and promoted rapid class switching to IgG compared to species B and D vectors. Serotype-switched regimens further enhanced antibody levels via intramuscular or intranasal routes and generated robust T cell responses when delivered intramuscularly. Intranasal vaccination induced detectable IgA but no measurable T cell responses, indicating route-dependent immune compartmentalization. Sera partially inhibited viral entry in a dose-dependent manner, with the greatest reduction observed in the Ad5/Ad6 regimen. Collectively, adenoviral species selection, serotype switching, and route of administration significantly influence GP-specific immunity and warrant further evaluation in protective challenge models.
2026-09-07 | Pan-Ebolavirus nanoparticle vaccine provides protection in rodents from lethal infection by Zaire and Sudan viruses.
Both Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) are members of the genus Ebolavirus and cause outbreaks marked by high fatality rates and repeated spillover from animal reservoirs. Filoviral glycoproteins (GPs) are the primary targets of neutralizing antibodies and form the basis of current vaccines. Here we describe the design, structural characterization, and evaluation of two-component self-assembling icosahedral I53-50 nanoparticles displaying prefusion EBOV or SUDV GP antigens, either individually or in cocktail and mosaic multivalent formats. EBOV-GP-I53-50 and SUDV-GP-I53-50 nanoparticles elicited strong homologous protection in mice and guinea pigs. In the mouse-adapted EBOV model (maEBOV), mosaic and cocktail formulations produced weak survival below that of the matched EBOV-GP-I53-50 GP immunogen. In contrast, in the gpaSUDV guinea pig model (gpSUDV), cocktail and mosaic nanoparticles elicited robust protection against gpSUDV, and detectable antibody responses to both SUDV and EBOV GPs. These findings demonstrate that multivalent GP-I53-50 nanoparticle immunogens can protect rodents from death, severe clinical signs of disease, and weight loss in relevant models. Together with the established clinical safety of the I53-50 platform, these results support continued efforts toward the development of a pan-ebolavirus vaccine.
2026-08-13 | 'Mismatched' Ebola vaccine may soon be rolled out widely.
Opinions shift after new data suggest vaccine for Ebola Zaire may also protect against Bundibugyo.
2026-06-05 | Cross-reactive Bundibugyo antibody responses after licensed Ebola vaccines.
The ongoing Bundibugyo virus disease (BDBV) outbreak in Central Africa highlights the absence of approved vaccines specifically targeting BDBV. Whether licensed Zaire ebolavirus (EBOV) vaccines induce cross-reactive immunity against BDBV remains largely unknown. We performed an immunogenicity analysis using serum samples from participants enrolled in the PREVAC randomized clinical trial evaluating licensed Ebola vaccine strategies in West Africa. Samples collected at day 28 (D28) and month 3 (M3) following vaccination with rVSVΔG-ZEBOV-GP or Ad26.ZEBOV/MVA-BN-Filo were assessed using a multiplex Luminex assay against glycoproteins from multiple filoviruses, including EBOV Kikwit, EBOV Mayinga, BDBV, Sudan virus, Reston virus, and Marburg virus. A total of 179 samples were analysed. Detectable cross-reactive antibody responses against BDBV were observed across vaccine groups, timepoints, and age categories. However, BDBV responses remained substantially lower than homologous EBOV responses. In rVSV recipients, median BDBV responses (net MFI) reached 282 (IQR 164-644) at D28 compared with 1788 (832-3311) against the homologous Kikwit antigen. Similar patterns were observed following rVSV booster vaccination and Ad26.ZEBOV/MVA-BN-Filo vaccination. The heterologous Ad26/MVA regimen demonstrated increasing BDBV responses between D28 and M3. Licensed EBOV vaccines induced detectable but quantitatively reduced cross-reactive antibody responses against BDBV. Although no direct assessment of vaccine efficacy against BDBV disease was possible, these findings support the plausibility of partial heterologous immunity following EBOV vaccination. In the absence of approved BDBV-specific vaccines, these data support the urgent evaluation of currently available Ebola vaccines during BDBV outbreaks and reinforce the importance of developing broadly protective pan-filovirus vaccines.
2026-06-04 | Pan-pathogen vaccine approaches: Toward broad-spectrum immunity in a One Health era.
Emerging and re-emerging infectious diseases (EIDs) represent an escalating threat to global public health, as exemplified by outbreaks of COVID-19, Ebola, Zika, and other zoonotic viruses. Traditional pathogen-specific vaccines, although effective for individual diseases, face significant limitations in addressing EIDs due to long development timelines, resource intensity, and restricted adaptability to novel pathogens or variants. Pan-pathogen vaccines-designed to provide broad-spectrum immunity across multiple related or unrelated pathogens-offer a transformative approach to pandemic preparedness. This review presents a comprehensive overview of pan-pathogen vaccinology within the One Health framework, emphasizing the integration of human, animal, and environmental health for proactive disease prevention. We provide explicit definitions for "universal", "broad-spectrum", and "pan-pathogen" vaccines and embed the One Health principle into the full vaccine development lifecycle through real-world case studies, including Nipah virus and rVSV-Ebola. The review highlights strategies for epitope discovery using comparative genomics, evolutionary biology, and immunoinformatics to identify conserved antigenic regions, and details mechanisms of cross-protective immunity mediated by T cells, broadly neutralizing antibodies, mucosal responses, and trained innate immunity with emphasis on their interplay. Advanced vaccine platforms-mRNA, viral vectors, protein subunits, and nanoparticle-based systems-are evaluated for their capacity to deliver multivalent, chimeric, and mosaic antigens. Preclinical and clinical advances against influenza, coronaviruses, flaviviruses, filoviruses, and critically, bacterial, fungal, parasitic, and DNA virus targets are summarized. Ethical, regulatory, and global health considerations for equitable vaccine distribution are discussed, with expanded safety analysis addressing pan-pathogen-specific hazards such as antigenic competition, autoimmunity, and regulatory adaptation. Persistent gaps, including antigenic variability, immune imprinting, safety concerns, and challenges in clinical validation, are identified, alongside controversies surrounding the balance between broad coverage and potential immune escape. Integrating genomic surveillance, predictive modeling, and emerging technologies such as artificial intelligence, systems biology, and synthetic vaccinology is essential to optimize vaccine design and accelerate translational implementation. Collectively, pan-pathogen vaccines represent a proactive, adaptive, and globally coordinated strategy to mitigate future pandemics and strengthen long-term health security.
small molecules
2026-09-23 | An expanded hypothesis: The role of ascorbate and glucose in the intracellular processes and immunobiology of Ebola virus haemorrhagic fever
The opposing effects of glucose and ascorbate transport on physiological processes may help explain Ebola virus disease pathophysiology. The virus impairs intracellular interferon (IFN) signalling. High plasma glucose levels contribute to oxidative stress and may also inhibit IFN signalling. Conversely, ascorbate may counteract the virus-mediated IFN blockade and interfere with viral budding. Dysregulation of glucose and ascorbate homeostasis may contribute to the pathophysiology of Ebola virus haemorrhagic fever by promoting oxidative stress, activation of the nuclear factor kappa B (NF-κB) pathway, and a cytokine storm. Hyperglycaemia commonly occurs in critically ill patients with Ebola virus haemorrhagic fever. Therefore, haemorrhagic fever syndrome could be understood as a state of oxidative stress driven by hyperglycaemia, NF-κB pathway activation, and inflammatory cytokines. A potential treatment strategy would focus on administering ascorbate and glutathione, together with glucose or insulin as appropriate, to maintain normal, stable plasma glucose levels and combat oxidative and inflammatory stress.
2026-07-28 | PTPN13 Contributes to Ebola Virus-Induced Immune Dysregulation via Dephosphorylation of IRF3 and PI3K-p85.
Ebola virus disease (EVD) is characterized by immune dysregulation and damaging hyperinflammation. We aimed to characterize the signaling pathways and regulatory mechanisms dysregulated during EVD. To avoid hyperinflammation, innate immune signaling is regulated by post-translational modifications (PTMs), including protein phosphorylation. Here, we show that the protein tyrosine phosphatase nonreceptor type 13 (PTPN13) negatively regulates Interferon (IFN)-β while also positively regulating the neutrophil chemoattractant CXCL1. Using vectors encoding IRF3 with mutations on phosphorylation sites, we identified Y292 on IRF3 as a PTPN13 target of dephosphorylation. Knockout of PTPN13 increased IRF3 phosphorylation and expression of IFNβ and IFN-stimulated genes (ISGs) following poly(I:C) stimulation. Intriguingly, depletion of PTPN13 during Ebola virus (EBOV) infection resulted in decreased IFNβ and ISG induction at later time points post-infection, which correlated with increased viral titers. We identified PTPN13-mediated dephosphorylation of the viral protein VP35 as one potential mechanism inhibiting virus replication. Additionally, the induction of inflammatory chemokines, including CXCL1, decreased in PTPN13 knockout cells late during EBOV infection. These effects could be explained by increased phosphorylation of the regulatory p85 subunit of PI3K. Dephosphorylation of p85 promotes its degradation, subsequently enhancing PI3K kinase activity and downstream signaling via AKT. Together, our study suggests that PTPN13 is involved in immune regulation and efficient antiviral responses by dephosphorylation of IRF3, EBOV-VP35 and PI3K-p85.
2026-07-17 | AI-Driven Discovery and BSL-4 Validation of Cross-Filovirus Ebola-Marburg Inhibitors and their Synergistic Combinations.
Filovirus outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV), pose severe global health threats characterized by high rates of fatal hemorrhagic fever. While species-specific vaccines and therapeutic monoclonal antibodies are approved for Zaire ebolavirus, broadly-active therapeutics remain unavailable, leaving populations vulnerable to MARV and other pathogenic Ebola species, such as Bundibugyo (BDBV) and Sudan (SUDV) ebolaviruses. Here we report a computationally guided, infectious virus validated screening platform for the rapid discovery of broad-spectrum filovirus antivirals. By leveraging quantitative structure- activity relationship (QSAR) models, we screened 142,382 compounds in silico to prioritize 125 high-potential candidates. Subsequent dose-response and viability profiling identified 23 compounds exhibiting potent, low-micromolar pan-filovirus activity and favorable cytotoxicity profiles. Molecular docking indicates these compounds target conserved structural and functional domains-primarily the VP35 and L proteins-which may disrupt essential viral replication and immune antagonism. Furthermore, systematic combinatorial screening revealed three highly synergistic compound pairs, notably NCGC00113249-01 and NCGC00118008-01, demonstrating robust cross-species efficacy. By targeting conserved vulnerabilities across the filovirus family, this integrated in silico and in vitro pipeline provides a scalable framework to rapidly nominate and optimize synergistic therapeutic regimens against both endemic and emerging viral threats including BDBV.
2026-06-28 | A New Proposal for Host-Directed Therapy in Ebola Virus Disease: Ozone Autohemotherapy as an Adjunctive Approach Within a Systems Biology Framework
Ebola Virus Disease (EVD) remains one of the most lethal viral hemorrhagic fevers, with mortality driven not only by viral replication but also by a dysregulated host response characterized by hyperinflammation, endothelial dysfunction, coagulopathy, metabolic derangement and multi-organ failure. Although monoclonal antibodies and vaccination have substantially improved outcomes, currently available interventions primarily target the virus and do not directly address the complex host-response networks that contribute to advanced disease and mortality. Here, we propose a systems biology framework for evaluating Ozone Autohemotherapy (O₃-AHT), specifically Major Autohemotherapy (MAH), as a host-directed adjunctive strategy in EVD. The framework is based on the capacity of O₃-AHT to generate controlled redox signals through Reactive Oxygen Species (ROS) and Lipid Ozonation Products (LOPs), which activate adaptive stress-response pathways including the Nrf2/Keap1/Antioxidant Response Element (ARE) system, the AMP-Activated Protein Kinase (AMPK)-Forkhead Box O (FOXO)-mechanistic Target of Rapamycin (mTOR)-sirtuin 1 (Sirt1) axis and Nrf2-mediated modulation of Nuclear Factor Kappa B (NF-κB) signaling. These interconnected pathways regulate antioxidant defenses, mitochondrial adaptation, autophagy, inflammatory responses, endothelial homeostasis and immune regulation-biological processes that intersect with major pathogenic mechanisms of EVD. Particular attention is given to Heme Oxygenase-1 (HO-1), a downstream effector of Nrf2 activation for which experimental evidence demonstrates suppression of Ebola virus replication in-vitro, providing a mechanistic bridge between host-directed redox modulation and antiviral activity. By integrating current knowledge from virology, immunology, redox biology and systems medicine, this framework identifies multiple points of convergence between ozone-induced adaptive signaling and Ebola pathophysiology. This work does not establish clinical efficacy but presents a hypothesis-generating model intended to guide future experimental investigation. As a conceptual framework, it proposes O₃-AHT as a candidate host-directed adjunctive approach that warrants systematic evaluation in preclinical models of Ebola virus disease.
2026-06-17 | Molecular phenotypes of sex and age specific differences relating to outcome in patients with Ebola virus disease.
Ebola virus (EBOV) causes a severe, potentially fatal, disease, with outcome likely related to both viral and host factors. There is a clear correlation between viral load and outcome (survival/death) and inflammatory as well as other cellular pathways are differentially activated in the acute stage between patients who go on to survive versus those who go on to die. Age and sex may influence the course of Ebola virus disease (EVD) with potential differences at the molecular level. To investigate whether there were age and/or sex-specific differences in patients with EVD, previously published data from an RNAseq analysis of the blood transcriptome in patients from the 2013-2016 West African outbreak was stratified according to age/sex of the individual. This was correlated with the outcome of infection. Similar to the previously published data, immune responses were downregulated during the acute phase in hospitalised survivors compared to hospitalized fatal cases, regardless of the sex of the patient. However, aspects of the blood transcriptome/host response differed between females and males and certain age groups at the transcriptomic level. Genes associated with the lymphocyte differentiation pathway decreased in expression level with age in hospitalised fatal cases. However, this was the opposite in hospitalised survivors. From a medical countermeasure perspective, the work indicated that selection of animal models should consider age and sex, depending on the research question, and cellular pathways were identified that could be chemotherapeutically enhanced to promote survival.
proteins
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-06-25 | Development of Peptide Entry Inhibitors Targeting the Endosomal Receptor NPC1 Binding Site of Orthoebolavirus.
Orthoebolavirus causes severe Ebola virus disease (EVD) and deadly outbreaks in humans. This infection occurs through macropinocytosis and trafficking to late endosomes or lysosomes that utilize the receptor Niemann-Pick C1 (NPC1) to enter the cell cytoplasm. We designed peptide inhibitors based on the NPC1 receptor to target the NPC1 binding site to block viral entry. The results indicated that the ligand-based peptide inhibitors showed potent inhibition activities in vitro studies against pseudotyped or replication-competent Orthoebolavirus. Therefore, we further evaluated one of them in a mouse model challenged with mice-adapted Ebola viruses, which showed some protection efficacy compared with the control group. This study suggests that ligand-based peptides are encouraging inhibitors in the development of inhibitors against Ebola virus infection.
2026-05-18 | Multivalent mRNA vaccine platform with compatible antigens conferred broad-spectrum protection against orthoebolaviruses' exposure.
Several orthoebolaviruses have been established, including Orthoebolavirus zairense [for Ebola virus (EBOV)], Orthoebolavirus sudanense [for Sudan virus (SUDV)], and Orthoebolavirus bundibugyoense [for Bundibugyo virus (BDBV)]. Orthoebolaviruses are highly virulent pathogens that cause severe disease in humans. However, most existing vaccines primarily target EBOV, and fail to provide robust cross-protection against other lethal orthoebolaviruses. The development of a broad-spectrum vaccine has the potential to efficiently mitigate outbreaks caused by multiple orthoebolaviruses. In this study, we developed and evaluated a broad-spectrum mRNA vaccine, designated [GPs+NP]@LNP, formulated with a single lipid nanoparticle (LNP) platform to encapsulate a mixed mRNA payload encoding the glycoproteins (GPs) of EBOV, BDBV, and SUDV, along with the nucleoprotein (NP) of EBOV. This rational antigenic combination was designed to engage both humoral and cellular arms of the immune system. Consistent with this design, the compatibility of humoral immunity-driving GPs and cellular immune-dominating NPs supports complementary immune responses, which together are associated with broad and durable protection against EBOV, BDBV, and SUDV in animal models. Antigenic coordination within a single LNP formulation may therefore represent an effective strategy to optimize vaccine immunogenicity, protective effect, durability, and safety. Collectively, these findings highlight [GPs+NP]@LNP as a promising approach for the development of next-generation vaccines targeting multiple pathogenic orthoebolaviruses.
2026-04-27 | Griffithsin-mediated inhibition of cellular entry of hemorrhagic fever viruses and insights into its mechanisms.
Griffithsin (GRFT), a lectin derived from the red algae Griffithsia, is known as an antiviral agent that binds to high-mannose glycans on viral envelope glycoproteins (GPs). In this study, we evaluated the antiviral activity of GRFT against Ebola virus (EBOV), Marburg virus (MARV), Lassa virus (LASV), Lujo virus (LUJV), and Crimean-Congo hemorrhagic fever virus (CCHFV), all of which cause severe and often fatal hemorrhagic fevers in humans. GRFT effectively blocked the entry of these viruses into cells, with stronger inhibition observed against LASV, LUJV, and CCHFV than against EBOV and MARV. This inhibitory effect depended on the lectin activity of GRFT, as its mutant lacking glycan-binding function completely lost the ability to inhibit the entry of these viruses into cells. We found that GRFT induced aggregation of virus-like particles (VLPs) derived from EBOV and MARV, whereas this activity was not observed with LASV- and LUJV-derived VLPs. Most of the escape mutants of LASV and LUJV GPs exhibited amino acid substitutions that likely disrupted GRFT binding by removing glycosylation sites at positions 79 and 73, respectively. Interestingly, other substitutions close to these positions, although unrelated to glycosylation, also contributed to reduced inhibitory activity of GRFT, suggesting a unique recognition mode in which both sugar chains and adjacent amino acid residues constitute the binding site structure for GRFT. Overall, our results provide insights into mechanisms underlying the antiviral effects of GRFT and highlight lectin-related activities as a key feature for broad-spectrum antiviral agents targeting highly glycosylated envelope GPs. Emerging and re-emerging infectious diseases, including viral hemorrhagic fevers, pose a major global health threat due to their potential for widespread outbreaks. Currently, treatment options for such diseases are limited and often ineffective against newly emerging viruses. Here, we demonstrate that Griffithsin (GRFT), a naturally derived lectin from red algae, inhibits the entry of multiple hemorrhagic fever viruses into host cells. By blocking key processes of the viral entry mediated by envelope glycoproteins, lectins such as GRFT can exhibit broad antiviral activity that could potentially overcome the limitations of existing treatments against emerging viruses. Our findings emphasize that targeting sugar chains and adjacent structures on viral glycoproteins with GRFT could provide a therapeutic strategy against diverse viral species. Such an approach is particularly valuable for newly emerging viruses for which specific countermeasures have not yet been established.
2026-03-12 | Development of VP30-targeted nanoparticles using DPS4 fusion peptides for the inhibition of Ebola virus.
Multiple outbreaks of Ebola virus in West Africa have posed significant threats to global public health owing to its high pathogenicity and fatality rates. Current treatments for Ebola Virus Disease are limited, underscoring the imperative for novel antiviral therapies. VP30, a critical RNA synthesis factor, interacts with nucleoprotein (NP) to facilitate Ebola viral genome transcription and replication. Notably, the host ubiquitin-ligase retinoblastoma-binding protein 6 (RBBP6) binds to VP30 at the same interface as NP, thereby inhibiting VP30-NP interactions and indicating that targeting this interface could advance antiviral drug development. In this study, we engineered six peptide mutants through amino acid substitutions at key VP30 binding sites. These mutants were fused to DNA-binding protein from starved cells 4 (DPS4) to assemble nanoparticles, enabling surface display of the peptides. Antiviral effects were evaluated using minigenome and transcription and replication-competent virus-like particles (trVLPs) systems. Among the variants, RPL1 and NPL3 peptides exhibited relatively strong apparent affinities with the VP30 and potent antiviral activity by disrupting Ebola viral genome transcription and replication. To elucidate the binding details between the peptides and VP30, we determined crystal structures of complexes between RPL1 or NPL3 peptides and VP30 via X-ray crystallography. Concurrently, molecular dynamics (MD) simulations revealed the dynamic binding processes of these peptides to VP30. Structural analyses confirmed that the peptides bind to the VP30/NP interface and compete with NP. Our findings demonstrate that DPS4-fusion peptides effectively deliver peptides into cells as nanoparticles and inhibit VP30-NP interactions, presenting a novel antiviral strategy for Ebola virus.
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2026-07-17 | Ebola virus exploits host lncRNA LINC01740 to enhance ATF3 and suppress antiviral immune responses.
Ebola virus (EBOV) infection causes severe hemorrhagic fever marked by dysregulated cytokine production, impaired antiviral defenses, and multi-organ failure. Macrophages are primary targets of EBOV, and viral replication profoundly alters macrophage transcriptional programs, driving hyperinflammation. Although long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of immunity and viral pathogenesis, their roles in EBOV infection remain poorly understood. We performed comprehensive transcriptomic profiling of primary human monocyte-derived macrophages infected with the highly pathogenic EBOV Mayinga variant. Infection triggered extensive remodeling of both coding and non-coding transcriptomes, including hundreds of differentially expressed lncRNAs. Functional analysis of neighboring protein-coding genes of EBOV-induced lncRNAs (EVILs) revealed enrichment of pathways linked to cytokine signaling, transcriptional regulation, and cell signaling, all of which are central to Ebola virus disease (EVD) pathogenesis. Among the most strongly induced EVILs, LINC01740 and its neighboring protein-coding gene, Activating Transcription Factor 3 (ATF3), were significantly upregulated. Antisense oligonucleotide-mediated inhibition of LINC01740 reduced ATF3 mRNA and protein levels. CRISPR/Cas13d-mediated knockdown of ATF3 restored type I interferon (IFN-I) signaling and antiviral gene expression in EBOV-infected macrophages. Mechanistically, ATF3 functions as a negative regulator of IFN-I and type I interferon-stimulated gene expression, thereby suppressing antiviral immune responses in EBOV-infected macrophages. Together, these findings identify a previously unrecognized LINC01740-ATF3-IFN-I regulatory axis that EBOV exploits to promote immune suppression and viral replication.
2026-04-02 | leucine rich alpha-2-glycoprotein 1 (LRG1) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [68, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥ 0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [88, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [68, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of LRG1, some of which might be known to exist via wet labexperiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-12-23 | retinol dehydrogenase 13 (all-trans/9-cis) (RDH13) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [21, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [9, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [21, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of RDH13, some of which might be known to exist via wet lab experiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-11-28 | aldolase, fructose-bisphosphate A (ALDOA) : Machine learning discoveries of 2nd order combinations in peripheral blood mononuclear cells (PBMCs) strongly activated in fatal West African Ebola Virus (EBOV) Disease (EVD)
Background : The pathogenesis of human Ebola virus disease (EVD) is complex and to clarify how host responses contribute to EVD pathophysiology, [65, in ref., in-text cit. - 1] performed multi-platform ’omics analysis of peripheral blood mononuclear cells (PMBCs) and plasma from EVD patients. Their results pointed that EVD molecular signatures overlapped with those of sepsis, thus indicating that pancreatic enzymes contributed to tissue damage in fatal EVD, and suggested that Ebola virus infection might induce aberrant neutrophils (activities of which could explain hallmarks of fatal EVD). For this, they record Table S5 i.e file NIHMS922130-supplement-5.xlsx, in their supplementary, that contains the comparison for Fatalities vs. healthy controls (FvsH), to study the PMBC transcriptome data. This table contains a list of 11804 unique genes, for whom log2 fold change (logFC) and q-value (adj.P.Val), have been recorded. Due to limited computational power / resources, only genes that are (up/↑)-regulated with a logFC ≥0.3, which accounts to a total number of 3327, and genes that are (down/↓)-regulated with a logFC < -0.3, which accounts to a total number of 3529 genes, are considered. Issue : There are not much genomic studies which account for combinations of genes or factors that might be working synergistically in human EVD. Because, if that is done, it would open a range of insights into multiple factors that might be working synergistically at say, 2nd order level, to start with. These might help in developing therapeutics for the EVD, based on synergistic mechanisms. With this aim in mind, the idea of this current manuscript is to study the 2nd order rankings of genes in the FvsH case, using PMBC transcriptome data with respect to human EVD. Resolution : In a recently published work [20, in Ref., in-text Cit. - 2], a frame work of a search engine was developed which can rank combinations of factors (genes/proteins) in a signaling pathway. Adapted search engine to the data on EVD by [65, in Ref., in-text Cit. - 1], for FvsH case, reveals 2nd order combinations of ALDOA, some of which might be known to exist via wet lab experiments, while many are yet to be tested. The revealed combinations might help test possible hypotheses that might be the causing factors in EVD. Further, in my limited grasp, if proven true, these combinations might pave way for development of gene based therapies aimed at resolving pathological issues related to EVD.
2025-07-10 | Data Sheet 1_Single-cycle, pseudotyped reporter influenza virus to facilitate evaluation of treatment strategies for avian influenza, Ebola and other highly infectious diseases in vivo.pdf
The rapid spread of infectious diseases presents a significant global threat, with seasonal influenza viruses, leading to 290,000–650,000 deaths annually. Emerging high pathogenic influenza strains from animals such as H5N1 and H7N9 further exacerbates pandemic risks. While developing effective vaccines and therapeutics is critical, the evaluation of these interventions is constrained by the requirement for high biosafety containment facilities. To circumvent these challenges, we developed S-Lux, a replication-deficient, single-cycle recombinant influenza virus expressing firefly luciferase (Flux) as a reporter protein. S-Lux can be pseudotyped with haemagglutinin from avian influenza, H5 and H7, enabling real-time monitoring of viral infection in vivo, and facilitate therapeutic antibody evaluation in low-containment facilities. In mice, S-Lux infection resulted in dose-dependent bioluminescent expression in the mouse airways and allowed evaluation of neutralising monoclonal antibodies and clearance of infected cells in mice. To extend this system, we generated ES-Lux by pseudotyping with the Ebola Glycoprotein (GP) and demonstrated that ES-Lux can be used to evaluate the efficacy of Ebola GP-targeting antibodies in vivo. Together, S-Lux and ES-Lux enable robust, simple and time-efficient assessment of antiviral therapy targeting influenza and Ebola virus in vivo, overcoming biosafety constraints that limit traditional efficacy studies.
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Drug Discovery Landscape
22 orphan drug designations for Ebola hemorrhagic fever, including 2 approved therapies.
22 orphan drug designations for Ebola hemorrhagic fever, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
subunit protein vaccine of recombinantly expressed Sudan Ebola virus glycoprotein | vaccines | FDA | — | Soligenix, Inc. |
Rintatolimod | RNAs | FDA | — | AIM ImmunoTech Inc. |
Two immunoglobulin subclass 1 (IgG1) human monoclonal antibodies that target the Sudan ebolavirus glycoprotein | antibodies | FDA | — | Mapp Biopharmaceutical, Inc. |
ansuvimab | antibodies | FDA | Emergent Manufacturing Operations Baltimore LLC | |
atoltivimab, odesivimab and maftivimab | antibodies | FDA | Regeneron Pharmaceuticals, Inc. | |
quinacrine | small molecules | FDA | — | Collaborations Pharmaceuticals, Inc. |
ansuvimab-zykl [EBANGA™] | antibodies | FDA | Approved | Emergent Manufacturing Operations Baltimore LLC |
pyronaridine tetraphosphate | small molecules | FDA | — | Collaborations Pharmaceuticals, Inc. |
Three human monoclonal antibodies against the Ebola virus glycoprotein | antibodies | EMA | Regeneron Ireland Designated Activity Company (DAC) | |
tilorone dihydrochloride | small molecules | FDA | — | Collaborations Pharmaceuticals, Inc. |
Ranpirnase | proteins | FDA | — | Tamir Biotechnology, Inc. |
Monovalent replication-incompetent adenovirus serotype 26 (Ad26) vaccine, AD26.ZEBOV in combination with multivalent replication-defective Modified Vaccinia Ankara (MVA)-Bavarian Nordic (BN) vaccine, MVA-mBN226B | vaccines | FDA | Janssen Vaccines and Prevention B.V. | |
atoltivimab, maftivimab, and odesivimab-ebgn [INMAZEB™] | antibodies | FDA | Approved | Regeneron Pharmaceuticals, Inc. |
aphidicolin | small molecules | FDA | — | Biospherics.net LLC |
2-ethylbutyl (2S)-2-{[(S)-{[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl]methoxy}(phenoxy)phosphoryl]amino}propanoate | small molecules | EMA | Gilead Sciences Ireland UC | |
Porgaviximab | antibodies | EMA | — | Granzer Regulatory Consulting & Services GmbH |
Remdesivir | small molecules | FDA | Gilead Sciences, Inc. | |
Rintatolimod | RNAs | EMA | — | NV Hemispherx BioPharma Europe |
Fibrinogen-coated albumin spheres | other | EMA | — | Fibreu Limitless Research S.L. |
recombinant nematode anticoagulant protein c2 (rNAPc2) | proteins | FDA | — | ARCA Biopharma, Inc. |
monoclonal antibody consisting of three mouse/human chimeric IgG1 monoclonal antibodies (c2G4, c4G7, and c13C6) that target Ebola virus | antibodies | FDA | — | LeafBio, Inc. |
5'-GCCATGGTTTTTTCTCAGG-3' | antibodies | FDA | Sarepta Therapeutics, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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