RARE DISEASE
Nipah virus disease
Nipah virus disease
Nipah virus disease
Synonyms: Nipah encephalitis, Nipah fever
Synonyms: Nipah encephalitis, Nipah fever
Synonyms: Nipah encephalitis, Nipah fever
Drug discovery
1
drug
With orphan designation
Overview
Nipah virus (NiV) is a lethal bat-borne zoonotic pathogen causing severe encephalitis and respiratory disease, with transmission via infected animals, contaminated food, or direct human contact [1][6]. The incubation period ranges from 4–21 days, progressing rapidly to altered mental status, coma (40–75% mortality), and long-term neurological deficits in survivors [1][6][11]. No approved vaccines or treatments exist, though monoclonal antibodies and antivirals show therapeutic promise [3][13].
Population
Endemic in South/Southeast Asia (Bangladesh, India, Malaysia), with outbreaks linked to bat habitats and date palm sap consumption [2][7][10]
High-risk groups include agricultural workers, healthcare providers, and caregivers due to human-to-human transmission [12][15]
Relapsing/late-onset encephalitis occurs in 20% of survivors [1][17]
Categories: rare infectious diseases, rare neurological diseases
Research Papers
693 drug discovery papers about Nipah virus disease, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
693 drug discovery papers about Nipah virus disease, with 1 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-26 | Discovery of Quercetin as a Potential Entry Inhibitor of Nipah Virus: A Path Toward Antiviral Therapy.
Nipah virus (NiV) is a zoonotic virus that causes severe encephalitis and respiratory disease with a mortality rate often exceeding 70%. Currently, there are no licensed vaccines or therapeutics for NiV disease. This study aimed to identify and experimentally evaluate small-molecule inhibitors targeting the NiV-G (attachment) glycoprotein using integrated in silico and in vitro approaches. A high-throughput virtual screening of >215,000 compounds was conducted against the NiV-G glycoprotein, using docking and molecular dynamics (MD) simulations. The next potential candidates were evaluated using an established, BSL-2-compatible recombinant Cedar virus (rCedV)-based green fluorescent protein (GFP) reporter virus expressing the NiV-F (fusion) and G glycoproteins (rCedV-NiV-B-GFP). During MD simulations, quercetin demonstrated the most stable binding, maintaining a consistent RMSD (3.25 ± 0.3 Å). In vitro testing showed dose-dependent inhibition of rCedV-NiV-B-GFP infection. Although quercetin alone was less potent (IC50 = 24 µM; 95% CI: 7.6-93.6 µM) than a reference NiV-neutralizing monoclonal antibody mAb-7B7 (IC50 = 0.027 μg/mL; approximately 0.00018 μM; 95% CI: 0.0108 to 0.0735), combination with ascorbic acid enhanced neutralization (IC50 = 4.4 µM; 95% CI: 2.9-6.8 µM). Quercetin demonstrated a high Selectivity Index of >20.8. The study identifies quercetin as a promising small-molecule inhibitor of NiV cellular infection, potentially through a stable interaction with NiV-G at the ephrin-B2/B3 binding interface identified computationally. These findings highlight the importance of combining computational screening with BSL-2 cell-based bioassays to accelerate NiV countermeasure discovery.
2026-09-19 | Modeling Risk Group 4 virus infection and antiviral treatment in microfluidic lung organ-on-chips in maximum containment laboratories.
Development of candidate countermeasures against human pathogens frequently includes nonhuman animal experimentation. Preclinical animal pathogen exposure studies are conducted to model diseases and accumulate preliminary and hypothetically translatable data to inform and justify the design of clinical trial evaluation of countermeasure safety and efficacy. In addition to frequent ethical critiques, challenges associated with animal experimentation include considerable resources needed to achieve statistical power and robustness, replicability and reproducibility concerns, potentially compromised objectivity through lack of blinding, fundamental species-specific biological differences, and risk of unpredictable pathogen adaptation to the experimental animal. Recent U.S. and U.K. government initiatives aim to reduce animal experimentation by complementing or potentially replacing them with new approach methodologies (NAMs), i.e., increasingly sophisticated in silico, in chemico, and in vitro approaches. We piloted development of one type of NAM, organ-on-chips (OOCs), in the highly challenging environment of a maximum (biosafety level 4) containment laboratory. Using a Risk Group 4 virus, Nipah virus (NiV), and two types of lung OOCs seeded with human or porcine cells, we demonstrated the recapitulation of key features of NiV lung infection, including viral infection, replication, and translocation, that are associated with proinflammatory cytokine secretion, immune cell recruitment, and disruption of the air-liquid interface barrier. We reproduced the known anti-NiV activity of remdesivir and evaluated that of another potential antiviral, zotatifin. Our results pave the way for similar applications of advanced microphysiological systems for modeling infections caused by high-consequence viruses.
2026-09-04 | Structural Aspects of Nipah Virus Glycoproteins using Predictive Protein Modeling
Abstract Nipah is a virus borne zoonotic disease that mostly occurs in Southeast Asian countries. Nipah virus (NiV) infection is potentially lethal as it can cause fatal encephalitis, and as of now, there are no vaccines or therapeutic treatments for this disease. The highly pathogenic NiV belongs to the Paramyxovirus family and the natural host of NiV is fruit bats of the Pteropodidae family. Though NiV has not been detected in the US, rather recently the Camp Hill virus (CHV) in shrew species was identified in Camp Hill, Alabama. This virus is characteristically similar to Nipah, and belongs to the henipavirus genus that include the Nipah and Hendra viruses. NiV has two surface glycoproteins namely the attachment glycoprotein (NiVG) and the fusion glycoprotein (NiVF). Being associated with host cell attachment and fusion of viral membrane, these glycoproteins tend to facilitate the viral entry to the host cell. The present paper describes the structures of the aforesaid viral glycoproteins based on the available database of protein structures, and examines if they have an evolutionary link to other viral glycoproteins. Certain similar glycoproteins found in different countries are also explored. The structure-function relationship for these two NiV glycoproteins are determined using time-based molecular dynamics (MD) simulation. The interfacial ligand-receptor interactions between NiV proteins with human receptor and monoclonal antibody, Fab 66, are examined. A primary motivation for these structural studies is that the results might potentially contribute to future therapeutic developments and drug designs to effectively combat NiV.
2026-09-03 | Computational identification of multi-targeted bioactive phytocompounds as candidate drug molecules against Nipah virus infection
Nipah Virus (NiV) is a highly virulent zoonotic virus that leads to severe encephalitis and respiratory diseases with mortality rates estimated at 40–75%, sometimes up to 100% in specific outbreaks. NiV has outbreaks in South and Southeast Asia, particularly in Bangladesh, India, Philippines, Malaysia, Singapore, and so on. The WHO classifies NiV as a priority pathogen due to its high fatality rate, lack of approved antiviral drugs or vaccines, and pandemic potential spread by human-to-human transmission. Therefore, identifying novel therapeutic agents against NiV remains a critical global health priority now. Natural phytochemicals have gained increasing attention due to their diverse biological activities and, favorable safety profiles. In this study, we investigated 2271 unique phytocompounds as drug candidates induced from 261 medicinal plants having high antiviral activities through molecular docking interaction with the NiV G glycoprotein, F fusion protein, and L protein. Phytocompounds with significant binding affinity (< − 7.0 kcal/mol) were further assessed by, drug-likeness screening, ADME/T Profiling, network pharmacology, protein–ligand interaction analysis, density functional theory (DFT) calculations, and 100 ns MD simulation to investigate structural stability and interaction behavior. Docking results revealed strong binding affinity of several phytochemicals toward NiV proteins. Among which Absinthin, Cycloepiatalantin, and Diosgenin showed the most favorable interactions results. ADME/T analysis suggested high absorption, low predicted toxicity, and effective blood–brain barrier penetration. DFT analysis indicated a favorable electronic interaction potential of the phytochemicals. MD simulations suggested stable protein–ligand complexes supported by the following analysis, RMSD, RMSF, SASA, RoG, MM-PBSA, DCCM, and PCA. Overall, these findings suggest that these Phytocompounds may serve as potential candidates for further experimental validation as antiviral agents against NiV. Using large-scale Phytocompounds screening, this study identified candidate compounds with predicted bioactivity capable of interacting with NiV proteins, while helping to reduce the cost, time, and labor associated with conventional wet-laboratory experiments.
2026-08-11 | Dihydroorotate dehydrogenase inhibitors are potent antiviral agents against henipaviruses and arenaviruses.
Hendra virus (HeV) and Nipah virus (NiV) are zoonotic henipaviruses associated with high mortality and are classified as Biosafety Level 4 (BSL-4) agents. To identify small molecule inhibitors, we performed a cell-based high-throughput screening (HTS) of an antiviral compound library using recombinant Cedar virus (rCedV) as a non-pathogenic BSL-2 henipavirus surrogate. Hit compounds were evaluated by cytotoxicity and antiviral assays to determine CC50 and EC50 values. Among eleven primary hits, five compounds-Farudodstat, Atovaquone, PTC299, hDHODH-IN-7, and Brequinar-were prioritized based on antiviral potency. These compounds are known inhibitors of dihydroorotate dehydrogenase (DHODH), a host enzyme essential for de novo pyrimidine biosynthesis and viral RNA replication. To validate their mechanism of action, metabolite rescue assays were performed using intermediates from the pyrimidine biosynthesis pathway, demonstrating that pyrimidine metabolite supplementation reversed the antiviral activity of PTC299. In addition, the enantiomer of PTC299, a much weaker inhibitor of DHODH, was 100-fold less potent in the antiviral assay. Both experiments confirm that the antiviral effects of these compounds against rCedar virus are mediated through inhibition of pyrimidine biosynthesis. In contrast, the antiviral activity of mycophenolic acid, a purine biosynthesis inhibitor, was not reversed by pyrimidine metabolite supplementation. Four pyrimidine biosynthesis inhibitors demonstrated broad-spectrum antiviral activity across multiple virus families. Notably, PTC299 exhibited a selectivity index exceeding 500. Together, these in vitro findings indicate that DHODH inhibitors have potential as potent broad-spectrum host-directed antivirals, especially against high-consequence and emerging viruses.
vaccines
2026-09-06 | Multi-epitope design against emerging nipah virus towards peptide vaccine development.
The lack of an approved vaccine against Nipah virus (NiV), a highly fatal zoonotic pathogen causing severe neurological and respiratory disease, remains a major global health challenge. Therefore, it is of interest to design a multi-epitope vaccine targeting the NiV phosphoprotein (UniProt ID: Q9IK91). Conserved B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes were identified and selected based on antigenicity, immunogenicity and safety. The resulting vaccine construct was evaluated through structural modeling, TLR4 docking, codon optimization and immune simulation analyses. Thus, data shows the favorable stability, strong receptor interaction, efficient expression potential and the ability to elicit robust humoral and cellular immune responses.
2026-06-20 | Mechanistic and antigenic boundaries of Henipavirus and Parahenipavirus glycoproteins.
Henipaviruses, in the Paramyxoviridae family, includes the highly virulent Nipah virus that causes reoccurring outbreaks of deadly disease. Recent discoveries of Henipavirus-like species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized and prompted the reorganization of these viruses into the Henipavirus and Parahenipavirus genera. Here, to explore the limits of structural and antigenic variation in both genera, collectively referred to as HNVs, we construct an expanded, diverse panel of HNV fusion and attachment glycoproteins from non-redundant HNV strains that better reflect global HNV diversity. We express and purify the fusion protein ectodomains and the attachment protein head domains and study their biochemical and biophysical properties. We perform immunization experiments in mice, eliciting antibodies reactive to multiple HNV fusion proteins. Cryo-electron microscopy structures elucidate molecular determinants of differential pre-fusion state stability and higher order contacts. A crystal structure of the Gamak virus attachment head domain reveals an additional domain appended to the conserved 6-bladed, β-propeller fold. Taken together, these studies expand the known structural and antigenic limits of the HNVs, reveal cross-reactive epitopes within both genera and provide foundational data for the development of broadly reactive countermeasures.
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.
2026-05-29 | Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps.
The coronavirus disease 2019 (COVID-19) pandemic highlights the importance of identifying high risk pathogens, defining the immunity gaps and developing preemptive vaccination strategies. Here, we establish a high-resolution surrogate virus neutralization test detecting neutralizing antibodies against multiple virus families simultaneously, demonstrating good concordance with traditional assays. Extensive serosurveillance of pre-pandemic sera from different continents reveals low prevalence human exposures to different beta-coronaviruses, and identifies individuals with prior exposure to ACE2-binding MERS-like viruses. Furthermore, COVID-19 vaccination induces significant cross-neutralizing antibodies against clade 1b, 1c, and 3 but not clade 1a sarbecoviruses. Similarly, MERS and Nipah convalescent sera neutralize cognate viruses but have limited cross-neutralization against other related merbecoviruses and henipaviruses that utilize DPP4 and ephrin B2 receptors. Finally, a cross-clade prime-and-boost vaccination strategy using antigenically distinct antigens could induce broadly neutralizing antibodies against related viruses beyond vaccine antigens, supporting broad-spectrum beta coronavirus vaccine development.
2026-05-16 | Complete protection against lethal Nipah virus challenge by intranasal vaccination with bacteriophage T4 coupled with Nipah virus G or F protein.
Nipah virus (NiV) is a highly lethal zoonotic pathogen, causing disease that can spread between animals and people with a mortality rate about 40% to 70%. No commercially approved vaccines or therapeutics are available. In this study, novel NiV vaccines targeting the attachment glycoprotein (G) or fusion glycoprotein (F) of NiV were developed utilizing bacteriophage T4 as a carrier platform. The immune effects induced in mice by intranasal immunization (i.n.) and intramuscular injection (i.m.) show that i.n. immunization with bacteriophage T4 coupled with Nipah virus G or F protein can not only stimulate humoral immunity and cellular immunity, but also induce excellent mucosal immune responses. Complete protection against lethal NiV challenge was achieved in Syrian hamsters after intranasal immunization with either T4-G, T4-F, or the mixture of T4-G and T4-F (1:1). Due to its safety and modular versatility, the bacteriophage T4 carrier system presents a promising strategy for developing vaccines against NiV and other viruses.
proteins
2026-05-11 | Comparative immunogenicity of monomeric and tetrameric Nipah virus G glycoprotein-based vaccine candidates demonstrate robust antibody responses in both forms.
Nipah virus (NiV) is a highly pathogenic zoonotic virus with no licensed vaccine. The G surface glycoprotein of NiV plays a critical role in host cell attachment and is a prime vaccine target. In this study, we designed and expressed two soluble recombinant variants of the G glycoprotein-monomeric and tetrameric forms-using a mammalian expression system to preserve the native-like structure. Both proteins were biochemically stable as measured up to one month at temperatures ranging from 2 to 8 °C and - 20 °C. While the monomer had a higher yield in transient expression, the tetramer more closely mimicked the native multimeric architecture and showed better biophysical stability. BALB/c mice immunized with either variant, along with AddaVax adjuvant, generated robust, long-lasting antibody and neutralizing responses persisting up to six months. Collectively, our findings demonstrate the robust immunogenicity of both soluble monomeric and tetrameric G immunogens, with the monomeric form offering high scalability, underscoring their suitability as subunit vaccine candidates against Nipah virus.
2026-01-28 | Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.
Viral fusion proteins are indispensable mediators of viral entry that orchestrate the fusion of viral and host membranes, making them primary targets for antiviral interventions. Class I fusion proteins, displayed on the surface of enveloped viruses (such as HIV-1, RSV, SARS-CoV-2, Nipah, influenza, and Ebola viruses), share conserved structural features, including the fusion peptide or loop and heptad repeat regions. These elements are essential for the formation of the post-fusion six-helix bundle during membrane fusion. Peptide inhibitors that mimic heptad repeat motifs have consequently emerged as an effective strategy for blocking the fusion process. This review summarizes design strategies for such inhibitors and highlights how sequence and structural insights have enabled their optimization via α-helical stabilization, hydrocarbon stapling, lactam bridges, lipid conjugation, macrocyclization, and multivalency. Using representative examples across major viral systems, this review illustrates how these strategies have led to the development of potent, stable, and even broad-spectrum antiviral peptides. This review provides insights to guide the rational design of next-generation peptide-based fusion inhibitors targeting viral membrane fusion.
2025-12-29 | A highly potent, stable, and safe dePEGylated lipopeptide against Nipah virus and related henipaviruses.
Nipah virus (NiV) poses a significant threat owing to its high mortality and the lack of approved therapeutics. Targeting the conserved heptad repeat 1 (HR1) domain of the viral fusion (F) protein constitutes a promising antiviral strategy. Also, lipopeptides derived from the human parainfluenza virus 3 (HPIV3) heptad repeat 2 (HR2) regions inhibit NiV fusion by blocking formation of the critical six-helix bundle (6-HB); however, their efficacy has been impeded by the controversial use of PEGylation. To resolve these limitations, we employed our proprietary heptad repeat 2 C-terminal fragment (HR2-CF) peptide displacement strategy that eliminates PEG and overcomes the resultant steric hindrance. The lead dePEGylated lipopeptide, VQ-P1-C16, exhibited antiviral activity comparable to that of PEGylated lipopeptide, VIKI-PEG4-C16. Further introducing Glu (E) or Lys (K) mutations yielded VQ-P1-EK3-C16, which exhibited ultra-potent pseudotyped henipavirus inhibition at pM concentrations and increased fusion inhibition. Meanwhile, it protected newborn mice from pseudotyped NiV-Malaysia and NiV-Bangladesh infection in lungs and brains. Structural simulations and mechanistic studies demonstrated that VQ-P1-EK3-C16 adopts a helical conformation, exhibits high affinity for NiV-HR1, and inhibits NiV 6-HB formation. Moreover, VQ-P1-EK3-C16 showed significantly increased solubility, improved thermal stability, strengthened resistance to proteases, and extended serum half-life. These findings establish VQ-P1-EK3-C16 as a highly potent, stable, and safe fusion inhibitor with promising potential for the clinical development of therapeutics against NiV and related henipaviruses.
2025-12-26 | Peptide–Ligand Conjugate‐Based Immunotherapeutic Strategy Targeting Nipah Virus Glycoprotein G: A Novel Approach for Treating Virus Infection by Employing Host Innate Immune Response
ABSTRACT Since birth, the human immune system continuously adapts to environmental exposures, developing robust immunological memory against a diverse range of antigens and allergens. Leveraging this pre‐existing immunity, this study introduces a novel immunotherapeutic approach targeting the Nipah virus, a zoonotic pathogen with a high mortality rate and no approved vaccines or therapeutics to date. The NiV glycoprotein G (NiV‐G), essential for viral attachment and fusion with host cells, was identified as a prime therapeutic target. This study proposes a peptide ligand complex (PLC) that constitutes high‐affinity ligands of NiV‐G joined with immunogenic peptides for stronger host innate immune response by an oxime linker using high‐throughput virtual screening (HTVS) and molecular dynamics simulations, Bleomycin and Octreotide were selected as potent ligands for NiV‐G. These were conjugated via an oxime linker to peptides derived from Escherichia coli outer membrane proteins (OMPs), which exploit the natural antibody memory against E. coli , constituting approximately 0.057% of total serum immunoglobulins in healthy individuals. The ligand component of PLC binds specifically to NiV‐G, blocking viral entry, fusion, and preventing syncytia formation, an essential mechanism for cell‐to‐cell spread. Simultaneously, the peptide component activates immune effector mechanisms such as antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC), promoting the clearance of infected cells and free viral particles from circulation. Computational analyses confirmed the Safety, stability, and immunogenicity of the PLC components. This strategy presents a compelling alternative to conventional monoclonal antibody‐based therapies, which are often constrained by high production costs, storage limitations, restricted accessibility, and susceptibility to antigenic drift. By harnessing pre‐existing immune memory and redirecting it toward viral targets, the peptide ligand complex (PLC) offers a cost‐effective and adaptable therapeutic platform. Beyond addressing the challenges posed by Nipah virus, this approach holds potential for combating other hard‐to‐treat infectious diseases and even cancer by transforming natural immunity into a powerful and versatile tool for targeted immunotherapy.
2025-12-23 | Computational design and experimental characterization of mini-protein binders targeting Nipah, Langya and Measles virus receptor-binding domains
Abstract A lack of reagents represents a major bottleneck in pandemic preparedness and rapid vaccine development. It is therefore important to enable the design of reagents for use in the treatment and diagnosis of emerging viral diseases. Ideally, the design and identification platform is fast, can be performed by testing only a small number of candidates and enables a generally applicable strategy. In this study, we assessed the ability of recently developed computational protein design tools to establish such a workflow for validating paramyxovirus receptor-binding protein de novo binders as such reagents. The family Paramyxoviridae includes various members that cause severe disease and exhibit re-occurring zoonotic spillover events, with documented human infections over the past decades. We successfully designed, identified, and characterized mini-proteins targeting the receptor binding proteins of Nipah virus, Langya virus, and Measles virus while screening as few as 10-16 designs per target. The resulting functional binders have moderate to low nanomolar affinities and display high on-target specificity. We further showed that our most promising Nipah virus receptor-binding protein binder is able to inhibit human receptor binding in vitro and competes for an epitope that overlaps with that of the neutralizing antibody HENV-117. However, despite these promising results, this Nipah binder is only weakly neutralizing, preventing therapeutic applications. Nevertheless, we established a platform, applicable to rapidly generate diagnostically relevant proteins from only a small number of candidates, and developed novel reagents for the Paramyxoviridae family.
antibodies
2026-09-26 | Defining Challenge Conditions for Nipah Virus in the Syrian Golden Hamster Model: Effects of Dose, Exposure Route and Viral Strain.
Nipah virus (NiV) is a highly pathogenic zoonotic virus for which no licensed vaccines or therapeutics are currently available, necessitating well-characterised animal models to support countermeasure development. This study aimed to establish an appropriate challenge dose in the Syrian golden hamster model at the UK Health Security Agency (UKHSA), incorporating both intraperitoneal (i.p.) and intranasal (i.n.) routes of infection and two clinically relevant strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B). Due to a different challenge doses and susceptibilities of hamsters to NiV being reported in the literature, there is a prerequisite to define the model parameters upon establishment in a new facility. Dose-ranging studies were performed across multiple independent experiments assessing survival, clinical progression and histopathological outcomes. Challenge via the i.p. route produced consistent and severe disease using an infectious dose of 103 TCID50 for both strains. In contrast, animals were more susceptible to infection via i.n. challenge with a dose of 10 TCID50 resulting in uniform lethality. For both challenge routes, respiratory and neurological disease manifestations were observed. These distinct disease phenotypes were supported by histopathological findings and viral RNA distribution in affected organs. Differences between strains were evident, with NiV-B showing a tendency towards a broader pulmonary pathology at lower doses after i.n. challenge. Collectively, these findings demonstrate that challenge dose, route of exposure, and viral strain influence disease outcomes in the hamster model.
2026-08-05 | Climate Change and Disease Risk in Bangladesh: A Century-Scale Warming Trend, Day-by-Day Patterns, a Six-Disease Seasonal Synthesis, and the Albedo-Driven Glacier-Melt-to-Flood Pathway
A century-scale climate trend analysis for Bangladesh (CRU TS4.07, 1901-2022), district-level (n=64) mapping of recent climate extremes (2017-2025), a seven-disease seasonal risk synthesis drawing on this author's six prior Bangladesh One Health papers (HPAI, rabies, Nipah virus, Japanese encephalitis, dengue, acute watery diarrhea), and a literature review of the black-carbon/albedo Himalayan glacier-melt-to-flood pathway. Discloses a MERRA-2 reanalysis discontinuity found while validating NASA POWER daily climate data against station-based climatology, offered as a methods-transparency contribution. Code and data: https://github.com/khalilurrrahmanridoykhan/bangladesh-climate-disease-synthesis
2026-07-17 | Ephrin B2 and Ephrin B3 are receptors for a novel putative henipavirus with zoonotic potential.
Next-generation sequencing has accelerated the discovery of novel putative viruses in wildlife reservoirs, while identifying those with zoonotic potential remains challenging. In this study, we report the identification and characterization of Ailong virus, a novel putative henipavirus from previous bat metagenomes in China that utilizes human ephrin B2 (EFNB2) and EFNB3 as functional receptors. Using an integrated approach combining phylogenetic analysis, pseudotyped virus entry assays, antibody blockade assays, and structural modeling, we demonstrate that Ailong virus glycoprotein binds human EFNB2 and EFNB3 with high specificity, mediating pseudovirus entry into both human neuronal and respiratory epithelial cells. Structural analysis revealed the Ailong virus glycoprotein-EFNB2 interface closely resembling that of Nipah virus (NiV), with conservation of all critical receptor-binding residues. Moreover, AiV encodes an exceptionally large phosphoprotein, 1,033 amino acids in length, which is larger than any other known phosphoprotein in the subfamily Paramyxoviridae. Given its receptor usage, structural similarities to NiV, and efficient entry in human airway epithelia, Ailong virus is believed to pose a spillover risk.
2026-07-16 | Emerging Trends to Endemic Disease: Nipah Virus Infection in Bangladesh
Abstract not available. Green Life Med. Col. J 2026;11(2): 36-37
2026-06-19 | Nipah Virus: Current Understanding of Epidemiology, Pathogenesis, and Therapeutic Strategies -A Comprehensive Review
Background: Nipah Virus (NiV) is a zoonotic virus with very high pathogenicity. Due to its high death rate, wide host range, and potential to cause epidemic and pandemic spread, it has been acknowledged as a major global health issue. After its initial discovery during the outbreak in Malaysia and Singapore, several re-occurrences in South and Southeast Asia have highlighted the ongoing danger this virus poses. Various factors such as environmental changes, humans invading wildlife habitats, and increased human animal interactions have raised the risk of virus spillover and emergence of diseases. Objective: The present review was planned to be a summary of the existing knowledge about the epidemiology pathogenesis new developments in diagnostics, and treatments for Nipah virus infection, plus pointing out recent progress and research needs in the future. Methods: The study was a detailed overview of selected published literature related to Nipah virus research, through which a narrative review was carried out. Incident characteristics of Nipah virus, modes of transmission, viral pathogenicity symptoms diagnostics, genomic monitoring, and treatment options were the main focus areas of research papers published from 2019 to 2026, that have been used in the study. The Chosen findings were rearranged and integrated in a qualitative descriptive manner. Results: The literature we analyzed showed that the gig virus is still a big virus to humans since it can cause serious brain and lung problems and even death. The spread of the virus has changed from mainly animals carrying the disease to more people passing the disease to each other in the same areas where the virus is mostly found. The virus sticking to the ephrin molecules first is the main thing in the virus harm to the blood vessels, messing up the immune system, and the virus going to the brain effects. Disease monitoring and detection have been enhanced through significant advancements in diagnostic technologies, including molecular testing and genomic sequencing platforms. Currently, the main method of treatment is supportive management. Still, new therapeutic methods like antiviral agents, monoclonal antibodies, vaccine production, and other alternative methods are quite promising. Conclusion: The Nipah virus continues to be a major concern for public health, given its potential for causing major epidemics. To better prepare ourselves and minimize the effects of any future outbreaks, it is necessary to constantly upgrade our surveillance systems, ensure diagnostics are easily accessible, develop medicines, and carry out researches in various fields. There is no doubt that worldwide cooperation through an integrated One Health approach will are key in devising better strategies for prevention and control.
other
2026-08-26 | Epitope-Based Nipah Virus G and F Head-to-Head Dimer mRNA Vaccines Exhibit Distinct Immunogenicity and Immune Profiles.
Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure-guided "immune-focusing" strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine.
2026-05-27 | Heterologous Sequential mRNA Vaccination of Indian Rhesus Macaques Elicits Broad Binding and Neutralizing Antibody Responses Against Diverse Henipaviruses.
Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs-including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)-emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks.
2026-04-11 | QStrain: an interactive platform for viral genome analysis and nucleic acid therapeutic design.
BACKGROUND: QStrain is an integrated resource platform designed to facilitate viral genome analysis and the rational design of nucleic acid therapeutics. RESULTS: The system integrates reference-guided multiple sequence alignment of high-risk viral pathogens, including Severe Acute Respiratory Syndrome Coronavirus 2, Lassa virus, Severe Fever with Thrombocytopenia Syndrome virus, Middle East Respiratory Syndrome Coronavirus, Influenza A virus subtype H5N1 and H7N9, Nipah virus, Respiratory Syncytial Virus, and Dengue virus, with a growing database of viral genomes. QStrain provides versatile visualization modules such as frequency profiles, conservation scores, RNA expression patterns, and phylogenetic trees to enhance the interpretation of viral sequence variation. By identifying highly conserved genomic regions, QStrain supports the prediction of candidate therapeutic targets and enables the automated design of small interfering RNA (siRNA) and antisense oligonucleotides (ASOs). Additional features include off-target searching and 2D structure viewing for comprehensive assessment of therapeutic potential. CONCLUSIONS: Ultimately, QStrain ( https://qstrain.sookmyung.ac.kr ) provides a critical, user-friendly framework to accelerate the design pipeline of nucleic acid-based therapies, enhancing preparedness against current and future viral outbreaks.
2026-03-13 | A structure-based mRNA vaccine for Nipah virus in healthy adults: a phase 1 trial.
Nipah virus (NiV) is a highly pathogenic, zoonotic paramyxovirus with pandemic potential. No licensed vaccines or treatments are available. Therefore, we conducted a phase 1, first-in-human, open-label, dose-escalation trial of a lipid nanoparticle mRNA vaccine, mRNA-1215, encoding a chimeric pre-fusion F (Pre-F) protein linked to glycoprotein G of a NiV Malaysian strain. Forty healthy adults, who met eligibility criteria, were enrolled into the 10-, 25-, 50- or 100-μg dose groups with ten participants per group. Each participant received two doses of mRNA-1215, intramuscularly, at a 4-week interval except for one participant in the 10-μg dose group who received only the first dose. All participants remained in the study until their final study visit. The primary outcome of vaccine safety and tolerability was determined by prespecified end points: the frequency and severity of solicited local and systemic adverse events (AEs), unsolicited AEs, safety laboratory measures, medically attended AEs, AEs of special interest, new chronic medical conditions and serious AEs. The most frequently reported local and systemic AEs were mild pain and tenderness at the injection site (n = 33; 82%) and mild malaise (n = 16; 40%), respectively. Overall, the vaccine was well tolerated. No serious AEs occurred during the study. mRNA-1215 elicited robust Pre-F and G binding antibody titers, the prespecified secondary end points. An exploratory analysis found that mRNA-1215 elicited neutralizing titers by 2 weeks after the prime in all dose groups. Responses increased after the boost and remained elevated for at least 1 year after vaccination. These findings demonstrate an initial overall favorable safety profile and immunogenicity results for a first-in-human, structure-based, chimeric mRNA Nipah virus vaccine. mRNA-1215 is a promising vaccine candidate for continued clinical development for populations at risk for regional and potentially larger outbreaks caused by Nipah virus. ClinicalTrials.gov identifier: NCT05398796 .
2026-03-02 | Next-Generation Vaccines and Antiviral Platforms: Molecular Advancements in the Struggle against Emerging Zoonotic and Viral Diseases.
The ongoing occurrence of zoonotic and viral diseases, such as SARS-CoV-2, H5N1, Nipah, and Ebola viruses, underscores the requirement for transformative innovations in vaccine and antiviral development. Classic vaccine technologies like inactivated or live-attenuated virus products have lengthy production cycles, cold-chain storage, and are poorly suited to reacting rapidly to emerging threats This review synthesizes the most recent advances in molecular virology, immunogen design, and biotechnology that will propel the next generation of prevention and treatment tools. We begin with the genomic and structural characteristics of high-consequence zoonotic viruses, highlighting the molecular determinants for virulence, host switching, and immune evasion. The review then provides a comparative review of the emerging vaccine platforms such as mRNA, DNA, viral vector, subunit, and inactivated vaccines based on design rationale, delivery systems, immunogenicity profiles, and global rollouts. At the same time, molecular mechanisms of antiviral drugs acting against viral polymerases, proteases, and entry mechanisms are discussed, and the new challenge of resistance evolution is emphasized. We also highlight recently developed molecular diagnostic tools like CRISPR-based tools, nanopore sequencing, and isothermal amplification technologies that are transforming real-time pathogen diagnosis in veterinary and human medicine. Last, the One Health aspect is introduced through veterinary applications of vaccines to zoonotic spillover prevention and antimicrobial resistance. In conclusion, this review gives a vision-orientated account of molecular strategies that bring together human and animal medicine to combat future pandemics. Our aggregated tables and visualizations are an asset for researchers, clinicians, and policymakers interested in the improvement of epidemic preparedness and cross-species disease surveillance.
small molecules
2026-09-26 | Discovery of Quercetin as a Potential Entry Inhibitor of Nipah Virus: A Path Toward Antiviral Therapy.
Nipah virus (NiV) is a zoonotic virus that causes severe encephalitis and respiratory disease with a mortality rate often exceeding 70%. Currently, there are no licensed vaccines or therapeutics for NiV disease. This study aimed to identify and experimentally evaluate small-molecule inhibitors targeting the NiV-G (attachment) glycoprotein using integrated in silico and in vitro approaches. A high-throughput virtual screening of >215,000 compounds was conducted against the NiV-G glycoprotein, using docking and molecular dynamics (MD) simulations. The next potential candidates were evaluated using an established, BSL-2-compatible recombinant Cedar virus (rCedV)-based green fluorescent protein (GFP) reporter virus expressing the NiV-F (fusion) and G glycoproteins (rCedV-NiV-B-GFP). During MD simulations, quercetin demonstrated the most stable binding, maintaining a consistent RMSD (3.25 ± 0.3 Å). In vitro testing showed dose-dependent inhibition of rCedV-NiV-B-GFP infection. Although quercetin alone was less potent (IC50 = 24 µM; 95% CI: 7.6-93.6 µM) than a reference NiV-neutralizing monoclonal antibody mAb-7B7 (IC50 = 0.027 μg/mL; approximately 0.00018 μM; 95% CI: 0.0108 to 0.0735), combination with ascorbic acid enhanced neutralization (IC50 = 4.4 µM; 95% CI: 2.9-6.8 µM). Quercetin demonstrated a high Selectivity Index of >20.8. The study identifies quercetin as a promising small-molecule inhibitor of NiV cellular infection, potentially through a stable interaction with NiV-G at the ephrin-B2/B3 binding interface identified computationally. These findings highlight the importance of combining computational screening with BSL-2 cell-based bioassays to accelerate NiV countermeasure discovery.
2026-09-19 | Modeling Risk Group 4 virus infection and antiviral treatment in microfluidic lung organ-on-chips in maximum containment laboratories.
Development of candidate countermeasures against human pathogens frequently includes nonhuman animal experimentation. Preclinical animal pathogen exposure studies are conducted to model diseases and accumulate preliminary and hypothetically translatable data to inform and justify the design of clinical trial evaluation of countermeasure safety and efficacy. In addition to frequent ethical critiques, challenges associated with animal experimentation include considerable resources needed to achieve statistical power and robustness, replicability and reproducibility concerns, potentially compromised objectivity through lack of blinding, fundamental species-specific biological differences, and risk of unpredictable pathogen adaptation to the experimental animal. Recent U.S. and U.K. government initiatives aim to reduce animal experimentation by complementing or potentially replacing them with new approach methodologies (NAMs), i.e., increasingly sophisticated in silico, in chemico, and in vitro approaches. We piloted development of one type of NAM, organ-on-chips (OOCs), in the highly challenging environment of a maximum (biosafety level 4) containment laboratory. Using a Risk Group 4 virus, Nipah virus (NiV), and two types of lung OOCs seeded with human or porcine cells, we demonstrated the recapitulation of key features of NiV lung infection, including viral infection, replication, and translocation, that are associated with proinflammatory cytokine secretion, immune cell recruitment, and disruption of the air-liquid interface barrier. We reproduced the known anti-NiV activity of remdesivir and evaluated that of another potential antiviral, zotatifin. Our results pave the way for similar applications of advanced microphysiological systems for modeling infections caused by high-consequence viruses.
2026-09-04 | Structural Aspects of Nipah Virus Glycoproteins using Predictive Protein Modeling
Abstract Nipah is a virus borne zoonotic disease that mostly occurs in Southeast Asian countries. Nipah virus (NiV) infection is potentially lethal as it can cause fatal encephalitis, and as of now, there are no vaccines or therapeutic treatments for this disease. The highly pathogenic NiV belongs to the Paramyxovirus family and the natural host of NiV is fruit bats of the Pteropodidae family. Though NiV has not been detected in the US, rather recently the Camp Hill virus (CHV) in shrew species was identified in Camp Hill, Alabama. This virus is characteristically similar to Nipah, and belongs to the henipavirus genus that include the Nipah and Hendra viruses. NiV has two surface glycoproteins namely the attachment glycoprotein (NiVG) and the fusion glycoprotein (NiVF). Being associated with host cell attachment and fusion of viral membrane, these glycoproteins tend to facilitate the viral entry to the host cell. The present paper describes the structures of the aforesaid viral glycoproteins based on the available database of protein structures, and examines if they have an evolutionary link to other viral glycoproteins. Certain similar glycoproteins found in different countries are also explored. The structure-function relationship for these two NiV glycoproteins are determined using time-based molecular dynamics (MD) simulation. The interfacial ligand-receptor interactions between NiV proteins with human receptor and monoclonal antibody, Fab 66, are examined. A primary motivation for these structural studies is that the results might potentially contribute to future therapeutic developments and drug designs to effectively combat NiV.
2026-09-03 | Computational identification of multi-targeted bioactive phytocompounds as candidate drug molecules against Nipah virus infection
Nipah Virus (NiV) is a highly virulent zoonotic virus that leads to severe encephalitis and respiratory diseases with mortality rates estimated at 40–75%, sometimes up to 100% in specific outbreaks. NiV has outbreaks in South and Southeast Asia, particularly in Bangladesh, India, Philippines, Malaysia, Singapore, and so on. The WHO classifies NiV as a priority pathogen due to its high fatality rate, lack of approved antiviral drugs or vaccines, and pandemic potential spread by human-to-human transmission. Therefore, identifying novel therapeutic agents against NiV remains a critical global health priority now. Natural phytochemicals have gained increasing attention due to their diverse biological activities and, favorable safety profiles. In this study, we investigated 2271 unique phytocompounds as drug candidates induced from 261 medicinal plants having high antiviral activities through molecular docking interaction with the NiV G glycoprotein, F fusion protein, and L protein. Phytocompounds with significant binding affinity (< − 7.0 kcal/mol) were further assessed by, drug-likeness screening, ADME/T Profiling, network pharmacology, protein–ligand interaction analysis, density functional theory (DFT) calculations, and 100 ns MD simulation to investigate structural stability and interaction behavior. Docking results revealed strong binding affinity of several phytochemicals toward NiV proteins. Among which Absinthin, Cycloepiatalantin, and Diosgenin showed the most favorable interactions results. ADME/T analysis suggested high absorption, low predicted toxicity, and effective blood–brain barrier penetration. DFT analysis indicated a favorable electronic interaction potential of the phytochemicals. MD simulations suggested stable protein–ligand complexes supported by the following analysis, RMSD, RMSF, SASA, RoG, MM-PBSA, DCCM, and PCA. Overall, these findings suggest that these Phytocompounds may serve as potential candidates for further experimental validation as antiviral agents against NiV. Using large-scale Phytocompounds screening, this study identified candidate compounds with predicted bioactivity capable of interacting with NiV proteins, while helping to reduce the cost, time, and labor associated with conventional wet-laboratory experiments.
2026-08-11 | Dihydroorotate dehydrogenase inhibitors are potent antiviral agents against henipaviruses and arenaviruses.
Hendra virus (HeV) and Nipah virus (NiV) are zoonotic henipaviruses associated with high mortality and are classified as Biosafety Level 4 (BSL-4) agents. To identify small molecule inhibitors, we performed a cell-based high-throughput screening (HTS) of an antiviral compound library using recombinant Cedar virus (rCedV) as a non-pathogenic BSL-2 henipavirus surrogate. Hit compounds were evaluated by cytotoxicity and antiviral assays to determine CC50 and EC50 values. Among eleven primary hits, five compounds-Farudodstat, Atovaquone, PTC299, hDHODH-IN-7, and Brequinar-were prioritized based on antiviral potency. These compounds are known inhibitors of dihydroorotate dehydrogenase (DHODH), a host enzyme essential for de novo pyrimidine biosynthesis and viral RNA replication. To validate their mechanism of action, metabolite rescue assays were performed using intermediates from the pyrimidine biosynthesis pathway, demonstrating that pyrimidine metabolite supplementation reversed the antiviral activity of PTC299. In addition, the enantiomer of PTC299, a much weaker inhibitor of DHODH, was 100-fold less potent in the antiviral assay. Both experiments confirm that the antiviral effects of these compounds against rCedar virus are mediated through inhibition of pyrimidine biosynthesis. In contrast, the antiviral activity of mycophenolic acid, a purine biosynthesis inhibitor, was not reversed by pyrimidine metabolite supplementation. Four pyrimidine biosynthesis inhibitors demonstrated broad-spectrum antiviral activity across multiple virus families. Notably, PTC299 exhibited a selectivity index exceeding 500. Together, these in vitro findings indicate that DHODH inhibitors have potential as potent broad-spectrum host-directed antivirals, especially against high-consequence and emerging viruses.
vaccines
2026-09-06 | Multi-epitope design against emerging nipah virus towards peptide vaccine development.
The lack of an approved vaccine against Nipah virus (NiV), a highly fatal zoonotic pathogen causing severe neurological and respiratory disease, remains a major global health challenge. Therefore, it is of interest to design a multi-epitope vaccine targeting the NiV phosphoprotein (UniProt ID: Q9IK91). Conserved B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes were identified and selected based on antigenicity, immunogenicity and safety. The resulting vaccine construct was evaluated through structural modeling, TLR4 docking, codon optimization and immune simulation analyses. Thus, data shows the favorable stability, strong receptor interaction, efficient expression potential and the ability to elicit robust humoral and cellular immune responses.
2026-06-20 | Mechanistic and antigenic boundaries of Henipavirus and Parahenipavirus glycoproteins.
Henipaviruses, in the Paramyxoviridae family, includes the highly virulent Nipah virus that causes reoccurring outbreaks of deadly disease. Recent discoveries of Henipavirus-like species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized and prompted the reorganization of these viruses into the Henipavirus and Parahenipavirus genera. Here, to explore the limits of structural and antigenic variation in both genera, collectively referred to as HNVs, we construct an expanded, diverse panel of HNV fusion and attachment glycoproteins from non-redundant HNV strains that better reflect global HNV diversity. We express and purify the fusion protein ectodomains and the attachment protein head domains and study their biochemical and biophysical properties. We perform immunization experiments in mice, eliciting antibodies reactive to multiple HNV fusion proteins. Cryo-electron microscopy structures elucidate molecular determinants of differential pre-fusion state stability and higher order contacts. A crystal structure of the Gamak virus attachment head domain reveals an additional domain appended to the conserved 6-bladed, β-propeller fold. Taken together, these studies expand the known structural and antigenic limits of the HNVs, reveal cross-reactive epitopes within both genera and provide foundational data for the development of broadly reactive countermeasures.
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.
2026-05-29 | Cross-clade vaccination to overcome sarbecovirus or merbecovirus neutralization gaps.
The coronavirus disease 2019 (COVID-19) pandemic highlights the importance of identifying high risk pathogens, defining the immunity gaps and developing preemptive vaccination strategies. Here, we establish a high-resolution surrogate virus neutralization test detecting neutralizing antibodies against multiple virus families simultaneously, demonstrating good concordance with traditional assays. Extensive serosurveillance of pre-pandemic sera from different continents reveals low prevalence human exposures to different beta-coronaviruses, and identifies individuals with prior exposure to ACE2-binding MERS-like viruses. Furthermore, COVID-19 vaccination induces significant cross-neutralizing antibodies against clade 1b, 1c, and 3 but not clade 1a sarbecoviruses. Similarly, MERS and Nipah convalescent sera neutralize cognate viruses but have limited cross-neutralization against other related merbecoviruses and henipaviruses that utilize DPP4 and ephrin B2 receptors. Finally, a cross-clade prime-and-boost vaccination strategy using antigenically distinct antigens could induce broadly neutralizing antibodies against related viruses beyond vaccine antigens, supporting broad-spectrum beta coronavirus vaccine development.
2026-05-16 | Complete protection against lethal Nipah virus challenge by intranasal vaccination with bacteriophage T4 coupled with Nipah virus G or F protein.
Nipah virus (NiV) is a highly lethal zoonotic pathogen, causing disease that can spread between animals and people with a mortality rate about 40% to 70%. No commercially approved vaccines or therapeutics are available. In this study, novel NiV vaccines targeting the attachment glycoprotein (G) or fusion glycoprotein (F) of NiV were developed utilizing bacteriophage T4 as a carrier platform. The immune effects induced in mice by intranasal immunization (i.n.) and intramuscular injection (i.m.) show that i.n. immunization with bacteriophage T4 coupled with Nipah virus G or F protein can not only stimulate humoral immunity and cellular immunity, but also induce excellent mucosal immune responses. Complete protection against lethal NiV challenge was achieved in Syrian hamsters after intranasal immunization with either T4-G, T4-F, or the mixture of T4-G and T4-F (1:1). Due to its safety and modular versatility, the bacteriophage T4 carrier system presents a promising strategy for developing vaccines against NiV and other viruses.
proteins
2026-05-11 | Comparative immunogenicity of monomeric and tetrameric Nipah virus G glycoprotein-based vaccine candidates demonstrate robust antibody responses in both forms.
Nipah virus (NiV) is a highly pathogenic zoonotic virus with no licensed vaccine. The G surface glycoprotein of NiV plays a critical role in host cell attachment and is a prime vaccine target. In this study, we designed and expressed two soluble recombinant variants of the G glycoprotein-monomeric and tetrameric forms-using a mammalian expression system to preserve the native-like structure. Both proteins were biochemically stable as measured up to one month at temperatures ranging from 2 to 8 °C and - 20 °C. While the monomer had a higher yield in transient expression, the tetramer more closely mimicked the native multimeric architecture and showed better biophysical stability. BALB/c mice immunized with either variant, along with AddaVax adjuvant, generated robust, long-lasting antibody and neutralizing responses persisting up to six months. Collectively, our findings demonstrate the robust immunogenicity of both soluble monomeric and tetrameric G immunogens, with the monomeric form offering high scalability, underscoring their suitability as subunit vaccine candidates against Nipah virus.
2026-01-28 | Structure-Guided Design of Peptide Inhibitors Targeting Class I Viral Fusion Proteins.
Viral fusion proteins are indispensable mediators of viral entry that orchestrate the fusion of viral and host membranes, making them primary targets for antiviral interventions. Class I fusion proteins, displayed on the surface of enveloped viruses (such as HIV-1, RSV, SARS-CoV-2, Nipah, influenza, and Ebola viruses), share conserved structural features, including the fusion peptide or loop and heptad repeat regions. These elements are essential for the formation of the post-fusion six-helix bundle during membrane fusion. Peptide inhibitors that mimic heptad repeat motifs have consequently emerged as an effective strategy for blocking the fusion process. This review summarizes design strategies for such inhibitors and highlights how sequence and structural insights have enabled their optimization via α-helical stabilization, hydrocarbon stapling, lactam bridges, lipid conjugation, macrocyclization, and multivalency. Using representative examples across major viral systems, this review illustrates how these strategies have led to the development of potent, stable, and even broad-spectrum antiviral peptides. This review provides insights to guide the rational design of next-generation peptide-based fusion inhibitors targeting viral membrane fusion.
2025-12-29 | A highly potent, stable, and safe dePEGylated lipopeptide against Nipah virus and related henipaviruses.
Nipah virus (NiV) poses a significant threat owing to its high mortality and the lack of approved therapeutics. Targeting the conserved heptad repeat 1 (HR1) domain of the viral fusion (F) protein constitutes a promising antiviral strategy. Also, lipopeptides derived from the human parainfluenza virus 3 (HPIV3) heptad repeat 2 (HR2) regions inhibit NiV fusion by blocking formation of the critical six-helix bundle (6-HB); however, their efficacy has been impeded by the controversial use of PEGylation. To resolve these limitations, we employed our proprietary heptad repeat 2 C-terminal fragment (HR2-CF) peptide displacement strategy that eliminates PEG and overcomes the resultant steric hindrance. The lead dePEGylated lipopeptide, VQ-P1-C16, exhibited antiviral activity comparable to that of PEGylated lipopeptide, VIKI-PEG4-C16. Further introducing Glu (E) or Lys (K) mutations yielded VQ-P1-EK3-C16, which exhibited ultra-potent pseudotyped henipavirus inhibition at pM concentrations and increased fusion inhibition. Meanwhile, it protected newborn mice from pseudotyped NiV-Malaysia and NiV-Bangladesh infection in lungs and brains. Structural simulations and mechanistic studies demonstrated that VQ-P1-EK3-C16 adopts a helical conformation, exhibits high affinity for NiV-HR1, and inhibits NiV 6-HB formation. Moreover, VQ-P1-EK3-C16 showed significantly increased solubility, improved thermal stability, strengthened resistance to proteases, and extended serum half-life. These findings establish VQ-P1-EK3-C16 as a highly potent, stable, and safe fusion inhibitor with promising potential for the clinical development of therapeutics against NiV and related henipaviruses.
2025-12-26 | Peptide–Ligand Conjugate‐Based Immunotherapeutic Strategy Targeting Nipah Virus Glycoprotein G: A Novel Approach for Treating Virus Infection by Employing Host Innate Immune Response
ABSTRACT Since birth, the human immune system continuously adapts to environmental exposures, developing robust immunological memory against a diverse range of antigens and allergens. Leveraging this pre‐existing immunity, this study introduces a novel immunotherapeutic approach targeting the Nipah virus, a zoonotic pathogen with a high mortality rate and no approved vaccines or therapeutics to date. The NiV glycoprotein G (NiV‐G), essential for viral attachment and fusion with host cells, was identified as a prime therapeutic target. This study proposes a peptide ligand complex (PLC) that constitutes high‐affinity ligands of NiV‐G joined with immunogenic peptides for stronger host innate immune response by an oxime linker using high‐throughput virtual screening (HTVS) and molecular dynamics simulations, Bleomycin and Octreotide were selected as potent ligands for NiV‐G. These were conjugated via an oxime linker to peptides derived from Escherichia coli outer membrane proteins (OMPs), which exploit the natural antibody memory against E. coli , constituting approximately 0.057% of total serum immunoglobulins in healthy individuals. The ligand component of PLC binds specifically to NiV‐G, blocking viral entry, fusion, and preventing syncytia formation, an essential mechanism for cell‐to‐cell spread. Simultaneously, the peptide component activates immune effector mechanisms such as antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC), promoting the clearance of infected cells and free viral particles from circulation. Computational analyses confirmed the Safety, stability, and immunogenicity of the PLC components. This strategy presents a compelling alternative to conventional monoclonal antibody‐based therapies, which are often constrained by high production costs, storage limitations, restricted accessibility, and susceptibility to antigenic drift. By harnessing pre‐existing immune memory and redirecting it toward viral targets, the peptide ligand complex (PLC) offers a cost‐effective and adaptable therapeutic platform. Beyond addressing the challenges posed by Nipah virus, this approach holds potential for combating other hard‐to‐treat infectious diseases and even cancer by transforming natural immunity into a powerful and versatile tool for targeted immunotherapy.
2025-12-23 | Computational design and experimental characterization of mini-protein binders targeting Nipah, Langya and Measles virus receptor-binding domains
Abstract A lack of reagents represents a major bottleneck in pandemic preparedness and rapid vaccine development. It is therefore important to enable the design of reagents for use in the treatment and diagnosis of emerging viral diseases. Ideally, the design and identification platform is fast, can be performed by testing only a small number of candidates and enables a generally applicable strategy. In this study, we assessed the ability of recently developed computational protein design tools to establish such a workflow for validating paramyxovirus receptor-binding protein de novo binders as such reagents. The family Paramyxoviridae includes various members that cause severe disease and exhibit re-occurring zoonotic spillover events, with documented human infections over the past decades. We successfully designed, identified, and characterized mini-proteins targeting the receptor binding proteins of Nipah virus, Langya virus, and Measles virus while screening as few as 10-16 designs per target. The resulting functional binders have moderate to low nanomolar affinities and display high on-target specificity. We further showed that our most promising Nipah virus receptor-binding protein binder is able to inhibit human receptor binding in vitro and competes for an epitope that overlaps with that of the neutralizing antibody HENV-117. However, despite these promising results, this Nipah binder is only weakly neutralizing, preventing therapeutic applications. Nevertheless, we established a platform, applicable to rapidly generate diagnostically relevant proteins from only a small number of candidates, and developed novel reagents for the Paramyxoviridae family.
antibodies
2026-09-26 | Defining Challenge Conditions for Nipah Virus in the Syrian Golden Hamster Model: Effects of Dose, Exposure Route and Viral Strain.
Nipah virus (NiV) is a highly pathogenic zoonotic virus for which no licensed vaccines or therapeutics are currently available, necessitating well-characterised animal models to support countermeasure development. This study aimed to establish an appropriate challenge dose in the Syrian golden hamster model at the UK Health Security Agency (UKHSA), incorporating both intraperitoneal (i.p.) and intranasal (i.n.) routes of infection and two clinically relevant strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B). Due to a different challenge doses and susceptibilities of hamsters to NiV being reported in the literature, there is a prerequisite to define the model parameters upon establishment in a new facility. Dose-ranging studies were performed across multiple independent experiments assessing survival, clinical progression and histopathological outcomes. Challenge via the i.p. route produced consistent and severe disease using an infectious dose of 103 TCID50 for both strains. In contrast, animals were more susceptible to infection via i.n. challenge with a dose of 10 TCID50 resulting in uniform lethality. For both challenge routes, respiratory and neurological disease manifestations were observed. These distinct disease phenotypes were supported by histopathological findings and viral RNA distribution in affected organs. Differences between strains were evident, with NiV-B showing a tendency towards a broader pulmonary pathology at lower doses after i.n. challenge. Collectively, these findings demonstrate that challenge dose, route of exposure, and viral strain influence disease outcomes in the hamster model.
2026-08-05 | Climate Change and Disease Risk in Bangladesh: A Century-Scale Warming Trend, Day-by-Day Patterns, a Six-Disease Seasonal Synthesis, and the Albedo-Driven Glacier-Melt-to-Flood Pathway
A century-scale climate trend analysis for Bangladesh (CRU TS4.07, 1901-2022), district-level (n=64) mapping of recent climate extremes (2017-2025), a seven-disease seasonal risk synthesis drawing on this author's six prior Bangladesh One Health papers (HPAI, rabies, Nipah virus, Japanese encephalitis, dengue, acute watery diarrhea), and a literature review of the black-carbon/albedo Himalayan glacier-melt-to-flood pathway. Discloses a MERRA-2 reanalysis discontinuity found while validating NASA POWER daily climate data against station-based climatology, offered as a methods-transparency contribution. Code and data: https://github.com/khalilurrrahmanridoykhan/bangladesh-climate-disease-synthesis
2026-07-17 | Ephrin B2 and Ephrin B3 are receptors for a novel putative henipavirus with zoonotic potential.
Next-generation sequencing has accelerated the discovery of novel putative viruses in wildlife reservoirs, while identifying those with zoonotic potential remains challenging. In this study, we report the identification and characterization of Ailong virus, a novel putative henipavirus from previous bat metagenomes in China that utilizes human ephrin B2 (EFNB2) and EFNB3 as functional receptors. Using an integrated approach combining phylogenetic analysis, pseudotyped virus entry assays, antibody blockade assays, and structural modeling, we demonstrate that Ailong virus glycoprotein binds human EFNB2 and EFNB3 with high specificity, mediating pseudovirus entry into both human neuronal and respiratory epithelial cells. Structural analysis revealed the Ailong virus glycoprotein-EFNB2 interface closely resembling that of Nipah virus (NiV), with conservation of all critical receptor-binding residues. Moreover, AiV encodes an exceptionally large phosphoprotein, 1,033 amino acids in length, which is larger than any other known phosphoprotein in the subfamily Paramyxoviridae. Given its receptor usage, structural similarities to NiV, and efficient entry in human airway epithelia, Ailong virus is believed to pose a spillover risk.
2026-07-16 | Emerging Trends to Endemic Disease: Nipah Virus Infection in Bangladesh
Abstract not available. Green Life Med. Col. J 2026;11(2): 36-37
2026-06-19 | Nipah Virus: Current Understanding of Epidemiology, Pathogenesis, and Therapeutic Strategies -A Comprehensive Review
Background: Nipah Virus (NiV) is a zoonotic virus with very high pathogenicity. Due to its high death rate, wide host range, and potential to cause epidemic and pandemic spread, it has been acknowledged as a major global health issue. After its initial discovery during the outbreak in Malaysia and Singapore, several re-occurrences in South and Southeast Asia have highlighted the ongoing danger this virus poses. Various factors such as environmental changes, humans invading wildlife habitats, and increased human animal interactions have raised the risk of virus spillover and emergence of diseases. Objective: The present review was planned to be a summary of the existing knowledge about the epidemiology pathogenesis new developments in diagnostics, and treatments for Nipah virus infection, plus pointing out recent progress and research needs in the future. Methods: The study was a detailed overview of selected published literature related to Nipah virus research, through which a narrative review was carried out. Incident characteristics of Nipah virus, modes of transmission, viral pathogenicity symptoms diagnostics, genomic monitoring, and treatment options were the main focus areas of research papers published from 2019 to 2026, that have been used in the study. The Chosen findings were rearranged and integrated in a qualitative descriptive manner. Results: The literature we analyzed showed that the gig virus is still a big virus to humans since it can cause serious brain and lung problems and even death. The spread of the virus has changed from mainly animals carrying the disease to more people passing the disease to each other in the same areas where the virus is mostly found. The virus sticking to the ephrin molecules first is the main thing in the virus harm to the blood vessels, messing up the immune system, and the virus going to the brain effects. Disease monitoring and detection have been enhanced through significant advancements in diagnostic technologies, including molecular testing and genomic sequencing platforms. Currently, the main method of treatment is supportive management. Still, new therapeutic methods like antiviral agents, monoclonal antibodies, vaccine production, and other alternative methods are quite promising. Conclusion: The Nipah virus continues to be a major concern for public health, given its potential for causing major epidemics. To better prepare ourselves and minimize the effects of any future outbreaks, it is necessary to constantly upgrade our surveillance systems, ensure diagnostics are easily accessible, develop medicines, and carry out researches in various fields. There is no doubt that worldwide cooperation through an integrated One Health approach will are key in devising better strategies for prevention and control.
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2026-08-26 | Epitope-Based Nipah Virus G and F Head-to-Head Dimer mRNA Vaccines Exhibit Distinct Immunogenicity and Immune Profiles.
Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure-guided "immune-focusing" strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine.
2026-05-27 | Heterologous Sequential mRNA Vaccination of Indian Rhesus Macaques Elicits Broad Binding and Neutralizing Antibody Responses Against Diverse Henipaviruses.
Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs-including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)-emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks.
2026-04-11 | QStrain: an interactive platform for viral genome analysis and nucleic acid therapeutic design.
BACKGROUND: QStrain is an integrated resource platform designed to facilitate viral genome analysis and the rational design of nucleic acid therapeutics. RESULTS: The system integrates reference-guided multiple sequence alignment of high-risk viral pathogens, including Severe Acute Respiratory Syndrome Coronavirus 2, Lassa virus, Severe Fever with Thrombocytopenia Syndrome virus, Middle East Respiratory Syndrome Coronavirus, Influenza A virus subtype H5N1 and H7N9, Nipah virus, Respiratory Syncytial Virus, and Dengue virus, with a growing database of viral genomes. QStrain provides versatile visualization modules such as frequency profiles, conservation scores, RNA expression patterns, and phylogenetic trees to enhance the interpretation of viral sequence variation. By identifying highly conserved genomic regions, QStrain supports the prediction of candidate therapeutic targets and enables the automated design of small interfering RNA (siRNA) and antisense oligonucleotides (ASOs). Additional features include off-target searching and 2D structure viewing for comprehensive assessment of therapeutic potential. CONCLUSIONS: Ultimately, QStrain ( https://qstrain.sookmyung.ac.kr ) provides a critical, user-friendly framework to accelerate the design pipeline of nucleic acid-based therapies, enhancing preparedness against current and future viral outbreaks.
2026-03-13 | A structure-based mRNA vaccine for Nipah virus in healthy adults: a phase 1 trial.
Nipah virus (NiV) is a highly pathogenic, zoonotic paramyxovirus with pandemic potential. No licensed vaccines or treatments are available. Therefore, we conducted a phase 1, first-in-human, open-label, dose-escalation trial of a lipid nanoparticle mRNA vaccine, mRNA-1215, encoding a chimeric pre-fusion F (Pre-F) protein linked to glycoprotein G of a NiV Malaysian strain. Forty healthy adults, who met eligibility criteria, were enrolled into the 10-, 25-, 50- or 100-μg dose groups with ten participants per group. Each participant received two doses of mRNA-1215, intramuscularly, at a 4-week interval except for one participant in the 10-μg dose group who received only the first dose. All participants remained in the study until their final study visit. The primary outcome of vaccine safety and tolerability was determined by prespecified end points: the frequency and severity of solicited local and systemic adverse events (AEs), unsolicited AEs, safety laboratory measures, medically attended AEs, AEs of special interest, new chronic medical conditions and serious AEs. The most frequently reported local and systemic AEs were mild pain and tenderness at the injection site (n = 33; 82%) and mild malaise (n = 16; 40%), respectively. Overall, the vaccine was well tolerated. No serious AEs occurred during the study. mRNA-1215 elicited robust Pre-F and G binding antibody titers, the prespecified secondary end points. An exploratory analysis found that mRNA-1215 elicited neutralizing titers by 2 weeks after the prime in all dose groups. Responses increased after the boost and remained elevated for at least 1 year after vaccination. These findings demonstrate an initial overall favorable safety profile and immunogenicity results for a first-in-human, structure-based, chimeric mRNA Nipah virus vaccine. mRNA-1215 is a promising vaccine candidate for continued clinical development for populations at risk for regional and potentially larger outbreaks caused by Nipah virus. ClinicalTrials.gov identifier: NCT05398796 .
2026-03-02 | Next-Generation Vaccines and Antiviral Platforms: Molecular Advancements in the Struggle against Emerging Zoonotic and Viral Diseases.
The ongoing occurrence of zoonotic and viral diseases, such as SARS-CoV-2, H5N1, Nipah, and Ebola viruses, underscores the requirement for transformative innovations in vaccine and antiviral development. Classic vaccine technologies like inactivated or live-attenuated virus products have lengthy production cycles, cold-chain storage, and are poorly suited to reacting rapidly to emerging threats This review synthesizes the most recent advances in molecular virology, immunogen design, and biotechnology that will propel the next generation of prevention and treatment tools. We begin with the genomic and structural characteristics of high-consequence zoonotic viruses, highlighting the molecular determinants for virulence, host switching, and immune evasion. The review then provides a comparative review of the emerging vaccine platforms such as mRNA, DNA, viral vector, subunit, and inactivated vaccines based on design rationale, delivery systems, immunogenicity profiles, and global rollouts. At the same time, molecular mechanisms of antiviral drugs acting against viral polymerases, proteases, and entry mechanisms are discussed, and the new challenge of resistance evolution is emphasized. We also highlight recently developed molecular diagnostic tools like CRISPR-based tools, nanopore sequencing, and isothermal amplification technologies that are transforming real-time pathogen diagnosis in veterinary and human medicine. Last, the One Health aspect is introduced through veterinary applications of vaccines to zoonotic spillover prevention and antimicrobial resistance. In conclusion, this review gives a vision-orientated account of molecular strategies that bring together human and animal medicine to combat future pandemics. Our aggregated tables and visualizations are an asset for researchers, clinicians, and policymakers interested in the improvement of epidemic preparedness and cross-species disease surveillance.
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Drug Discovery Landscape
1 orphan drug designation for Nipah virus disease.
1 orphan drug designation for Nipah virus disease.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
an immunoglobulin subclass 1 (IgG1) human monoclonal antibody that targets the Nipah virus fusion protein | antibodies | FDA | — | Mapp Biopharmaceutical, Inc. |
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