ETIDIOH - NEW

  Abstract Marburgviruses (MBVs) cause severe haemorrhagic fever with higher fatality rates than Ebola virus (EBOV). Here we show that the MBV glycoprotein (GP) mediates viral entry more efficiently than EBOV GP . Using cryo-EM , we determined structures of MBV GP in three states : (1) unbound; (2) bound to its endosomal receptor NPC1; and (3) complexed with a neutralizing nanobody . The glycan cap shields the receptor-binding site from NPC1 but only partially from the nanobody , enabling limited immune evasion . After glycan cap cleavage , NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity . NPC1 engagement also induces substantial conformational changes in MBV GP, probably facilitating membrane fusion . Furthermore, MBV GP is susceptible to the neutralizing nanobody , which mimics NPC1 at the receptor-binding site. Together, our findings reveal MBV GP as a highly efficient entry mediator and suggest...

  Abstract Enteroviruses, which belong to the family Picornaviridae, cause hand, foot, and mouth disease (HFMD), respiratory symptoms, and severe neurological complications in children . Since vaccines cannot provide cross-protection against different serotypes of enteroviruses , the development of broad-spectrum anti-enteroviral drugs is imperative . The viral 3C protease (3Cpro), which is essential for polyprotein processing represents a validated target for therapeutic intervention . Importantly, enterovirus 3Cpro shares conserved structural and catalytic features with coronavirus main protease (Mpro, also known as 3C-like protease, 3CLpro), providing a rationale for cross-target inhibitor repurposing . Through targeted screening of peptidomimetic protease inhibitors, a clinical-stage SARS-CoV-2 Mpro inhibitor was identified as a potent inhibitor of enterovirus A71 (EV71) 3Cpro. Bofutrelvir displayed nanomolar antiviral activity in multiple cell lines and demonstrated broad-spec...

  ABSTRACT Ferrets are widely used to model airborne transmission of influenza viruses in humans . Airborne transmission is evaluated by infecting donor ferrets with a high virus dose and monitoring transmission to contact animals sharing the same airspace . Humans can be infected with a broad range of influenza virus doses . Therefore, we evaluated the relationship between inoculation dose and transmission for two pandemic influenza viruses in ferrets . Donor ferrets were inoculated with 100 to 106 tissue culture infectious dose 50 (TCID50) of the 2009 pandemic H1N1 or 1968 pandemic H3N2 virus and were then paired with respiratory contacts . Using the proportion of donors that became infected across virus doses, we calculated the infectious dose 50 (ID50). Subsequently, by comparing the proportion of contacts that became infected, we calculated the transmissible dose 50% (TD50): the donor inoculation dose that resulted in transmission to 50% of contacts . For the 2009 pandemic H1N...

  Summary Background Lassa fever is one of the most important viral haemorrhagic fevers, yet post-discharge sequelae remain inadequately characterised . Previous studies have been limited by small sample sizes and unsystematic assessments. We aimed to describe post-discharge sequelae in Lassa fever survivors and explore the effect of disease severity on sequelae patterns. Methods LASCOPE was a prospective study of patients with PCR-confirmed Lassa fever hospitalised at Federal Medical Centre Owo, Owo, Nigeria , between April 23, 2018, and Feb 17, 2023. All patients who provided informed consent were included, with no age restriction. Severe disease was defined as the presence of at least one of the following during the acute phase: National Early Warning Score version 2 score of 7 or higher, Kidney Disease Improving Global Outcomes stage 2 or higher, or Lassa virus PCR Ct value of less than 25. At hospital discharge , follow-up of survivors was planned for day 60 after admission, o...

  Abstract We investigated the evolutionary history of the newly emergent neuraminidase (am4N1) associated with the D1.1 and D1.2 genotypes of highly pathogenic avian influenza A(H5N1) viruses in North America . Phylogenetic inference places am4N1 in a sister clade to Eurasian avian, swine, and human A(H1N1)pdm09 viruses and distinct from 1918, pre-2009 human seasonal, and classical swine A(H1N1) lineages . Am4N1 descends from diverse avian N1 genes endemic to the Americas. Phylodynamic analysis indicates a monophyletic am4N1 lineage with numerous introductions of viruses carrying the am4N1 gene likely originating from western Canada into the United States during emergence of the D1.1 and D1.2 genotypes. The lineage has diversified and accumulated deletions in the stalk domain . Despite amino acid divergence, structural modeling shows conserved neuraminidase architecture in the globular head . Given its distinct ancestry and amino acid sequence, further studies are needed to assess...

  Abstract Highly pathogenic influenza A viruses of the H5 subtype continue to diversify worldwide through mutation and genetic reassortment , generating novel variants with unpredictable consequences under the One Health approach . Between 2024 and 2025 , five outbreaks of avian influenza A viruses were detected in backyard poultry across Michoacán, Estado de México , and Ciudad de México . We conducted molecular and genetic characterization of five highly pathogenic H5N2 viruses isolated from these events. All cases tested positive for influenza A virus and the H5 hemagglutinin , exhibiting high pathogenicity with intravenous pathogenicity index values ranging from 2.88 to 3.0. Whole-genome sequencing revealed novel reassortants containing hemagglutinin from Eurasian H5N1 clade 2.3.4.4b and neuraminidase from the endemic Mexican H5N2 lineage . The viral genome of the isolate from Michoacán contained six segments derived from Eurasian H5N1 viruses introduced into North America in ...

  Summary Background The expanding mpox outbreak in Africa and travel-associated cases in other continents have increased efforts to vaccinate populations at high risk. This study aimed to assess serological immune responses 5 years after individuals received a primary vaccination (two-dose series) with the smallpox and mpox vaccine modified vaccinia Ankara-Bavarian Nordic (MVA-BN), as well as to evaluate the safety and immunogenicity of a third dose (booster). To date, there are no data for immunological memory or third-dose-induced immunity for MVA-BN at these long-term timescales. Methods In this open-label, prospective cohort extension, we re-enrolled health-care workers from a 2017 vaccination study in Bokungu Health Zone, DR Congo, to receive a third dose of MVA-BN. All previous participants were offered the opportunity to re-enrol. Participants were grouped according to whether they had received a childhood smallpox vaccination with a replication-competent vaccine strain (hi...

  Summary Background Mpox is a public health concern in eastern DR Congo . It continues to cause substantial numbers of hospital admissions , with changing demographics including children and adolescents , requiring comprehensive clinical and epidemiological investigation . In this study, we aim to describe the clinical characteristics of hospitalised participants infected with monkeypox virus (MPXV) subclade Ib/2023sh in the Kabare Territory in South Kivu , DR Congo. Methods This observational cohort study included patients admitted with suspected mpox to the reference centre of mpox treatment at Lwiro Hospital, South Kivu , DR Congo. Eligible participants must have had, at the time of inclusion, skin lesions compatible with the infection. Individuals who did not present lesions compatible with MPXV infection were also eligible if they had at least one of the following symptoms: fever, cervical lymphadenopathy, or pharyngitis , provided they had been in contact with someone with s...

  {Excerpt} (...) Results NAb geometric mean titers against H1N1 WI/22, H3N2 BA/22, H3N2 CR/23, H3N2-K BA/25, and H3N2-K NY/25 were 200, 231, 119, 50, and 60 at baseline and increased to 582, 661, 356, 85, and 119 at peak immunogenicity, respectively (...), reflecting a significant 2.86- to 2.99-fold increase in NAb titers against the prior H1N1 and H3N2 strains but a lower 1.70- to 1.98-fold increase in NAb titers against the H3N2-K strains . Baseline antibody titers to the H3N2-K strains were 2.0- to 4.6-fold lower than to the prior H1N1 and H3N2 strains (P < .001), and peak antibody titers to the H3N2-K strains following vaccination were 3.0- to 7.8-fold lower than to the prior H1N1 and H3N2 strains (P < .001). (...) Source:  Link:  https://jamanetwork.com/journals/jama/fullarticle/2846268?guestAccessKey=10f1c0a1-4189-438d-9f71-a588fdd0db53&utm_medium=email&utm_source=postup_jn&utm_campaign=article_alert-jama&utm_content=olf-tfl_&utm_term=0309...

  Abstract Background :  The emergence of the highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in North America , beginning in February 2022, has highlighted the dynamic, unpredictable, and regionally variable risk of infections . Studies are needed to assess the spatiotemporal clustering of HPAI H5 at the interface between wild waterfowl and commercial poultry to understand and mitigate this risk .  Methods :  Publicly available data on HPAI H5 detections in wild birds and commercial poultry from January 2022 to January 2026 were analyzed at the county level. Retrospective space-time permutation models were used to identify and scan for clusters with higher than expected detection rates.  Results :  A total of 17,091 HPAI H5 detections were reported in wild birds across 1,467 county-level locations. Four species , Mallard ( Anas platyrhynchos ) (2,848 detections, 16.66%), Canada goose ( Branta canadensis ) (1,496, 8.75%), Green-winged teal ( An...

  Abstract A human infection with clade 2.3.4.4b H5N1 influenza A virus in Canada revealed minority variants E190D and Q226H in the hemagglutinin (HA) receptor-binding site (RBS). Because mutations at positions 190 and 226 have been associated with altered receptor specificity in other influenza subtypes, we investigated their impact on receptor binding in H5 HA . Using a recombinant protein approach and an ELISA-based glycan-binding assay , we assessed binding to representative avian- and human-type sialylated glycans . Both single mutations and their combination resulted in a complete loss of detectable binding to the tested glycans . To evaluate whether this phenotype was background-dependent, Q226H was additionally introduced into two other H5 HA proteins , each representing a distinct clade . In both cases, the mutation similarly abolished receptor binding . These findings independently validate recent glycan microarray observations and demonstrate that the patient-derived E19...

  Abstract Highly pathogenic avian influenza (HPAI) viruses of H5N1 clade 2.3.4.4b, are spreading worldwide , posing a threat to wildlife, domestic animals, and humans . In 2025, a multidisciplinary collaboration for HPAI H5N1 surveillance among birds within Galveston County, Texas , was initiated. Between November and December 2025, oropharyngeal and cloacal swabs were collected from wild and domestic birds reported as dead or dying by Galveston County residents . Specimens were studied with molecular assays, Sanger sequencing, virus isolation, and next-generation sequencing. Molecular evidence of HPAI H5N1 was detected in 7 of 10 (70%) birds, and the virus was successfully cultured in MDCK cells . Next-generation sequencing analysis of eight influenza A genome segments demonstrated a 4:4 gene segment reassortant constellation within clade 2.3.4.4b, consistent with genotype D1.1. Community members exposed to HPAI were offered antiviral prophylaxis . No human infections were identi...

  Abstract Since 2020, H5Nx high pathogenicity avian influenza viruses (HPAIVs) have caused widespread disruptions not only to global agriculture and trade but also to the health of free-ranging wildlife . Pinnipeds have experienced greater mortality from H5Nx HPAIV than any other mammalian taxa . Emergent virus strains, persisting over long time periods and vast geographic distances , have repeatedly triggered large-scale mortality events in pinniped populations. Of particular concern is the spread of H5Nx HPAIV to the Southern Hemisphere —including the emergence of a marine mammal-adapted clade in South America and detections in the sub-Antarctic and Antarctic —and to other remote locations such as the Hawaiian Islands . These developments elevate concern for the world’s endangered, isolated and endemic pinnipeds . While managing HPAIV in any animal population is a formidable task, working with free-ranging marine mammals poses unique challenges. In this review and perspective pi...

  Ann Intern Med LIM SY, Lee J, Chang E, Kwon JS, et al Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical Trial. Ann Intern Med. 2026 Mar 3. doi: 10.7326/ANNALS-25-04883. PubMed           Abstract available Antiviral Res ZUO X, Xiao X, Dong X, Wang J, et al Direct-acting antivirals and beyond: emerging approaches to targeting viral RNA and ribonucleoprotein complexes. Antiviral Res. 2026;249:106383. PubMed           Abstract available RUDRAMURTHY GR, Gudla CS, Harisha R, Selvam V, et al FNDR-11124, a broad-spectrum small molecule inhibitor of viral RNA polymerase, restricts replication of SARS-CoV-2 and Influenza virus in vitro and in vivo. Antiviral Res. 2026 Mar 2:106382. doi: 10.1016/j.antiviral.2026.106382. PubMed           Abstract available Clin Infect Dis RIERA MT, Prato R, Perez-Rubio A, Ec...

  Ann Intern Med SACKS HS In older adults, high- vs. standard-dose influenza vaccine reduced hospitalization for influenza or pneumonia in those with CKD. Ann Intern Med. 2026 Mar 3. doi: 10.7326/ANNALS-26-00324. PubMed           Abstract available ANAND R, Glatt AE In healthy adults, a modified RNA vs. inactivated influenza vaccine reduced laboratory-confirmed influenza-like illness at >/=14 d. Ann Intern Med. 2026 Mar 3. doi: 10.7326/ANNALS-25-05681. PubMed           Abstract available Antiviral Res RUDRAMURTHY GR, Gudla CS, Harisha R, Selvam V, et al FNDR-11124, a broad-spectrum small molecule inhibitor of viral RNA polymerase, restricts replication of SARS-CoV-2 and Influenza virus in vitro and in vivo. Antiviral Res. 2026 Mar 2:106382. doi: 10.1016/j.antiviral.2026.106382. PubMed           Abstract available Arch Virol DUTTA M, Sarmah N, Siddique AI, Borah...

  Abstract Highly pathogenic avian influenza A H5N1 has recently expanded its mammalian host range ; in 2024, genotype B3.13 emerged in U.S. dairy cattle with pronounced mammary tropism . In the past, Influenza A virus immunology has been characterized primarily in respiratory infection models , whereas this study delineates immune responses after intramammary infection . An intramammary H5N1 challenge in Jersey cows in the early dry-off period enabled integration of dose- and compartment-resolved (alveoli versus teat cistern) cytokine and chemokine profiles with peripheral leukocyte dynamics and H5/N1-specific antibody responses. Infection-induced quarter-restricted, monophasic inflammatory networks peaking at 3 to 7 days post-infection , coordinated peripheral myeloid expansion and IFN gamma competent lymphocyte activation, and rising antibody titers across quarters. Competing Interest Statement The J.A.R. laboratory received support from Tonix Pharmaceuticals, Xing Technologies,...

  Abstract Background West Nile Virus (WNV) is a zoonotic arbovirus maintained in a transmission cycle between Culex mosquitoes and birds , occasionally spilling over into humans. The impact of avian biodiversity on WNV circulation remains debated, with studies reporting both negative and positive correlations (dilution and amplification effects respectively) across different settings. In Europe, this relationship remains largely unexplored, particularly in regions with high WNV transmission, such as Emilia-Romagna in Northern Italy. Methods We explored the association between avian biodiversity and WNV circulation in Culex mosquitoes in Emilia-Romagna using 11 years (2013–2023) of entomological surveillance data paired with two avian data sources . We calculated avian biodiversity indices (Shannon’s, Simpson’s, and Chao2) from observation records from the Farmland Bird Index project and applied linear regression models to assess their relationship with WNV detection frequency. Mor...

  Abstract Wastewater monitoring enables non-invasive, population-scale tracking of community infections independent of healthcare-seeking behavior and clinical diagnosis. Metagenomic sequencing extends this capability by enabling broad, pathogen-agnostic detection, genomic characterization , and identification of novel or unexpected threats . Here, we present data from CASPER (the Coalition for Agnostic Sequencing of Pathogens from Environmental Reservoirs), a U.S.-based wastewater metagenomic sequencing network designed for deep, untargeted pathogen monitoring at national scale. This release includes 1,206 samples collected between December 2023 and December 2025 from 27 sites across nine states , covering 13 million people . Deep sequencing (~1 billion read pairs per sample) generated 1.2 trillion read pairs ( 347 terabases ), enabling detection of even rare taxa , with CASPER representing 66% of all untargeted wastewater sequencing data currently available on the NCBI Sequence ...

  Abstract The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge , particularly for zoonotic H5N1 strains with pandemic potential . This study evaluates BECC470s, a synthetic TLR4 adjuvant , for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models . BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime–boost model . Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its po...

  Abstract Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals , heightening the risk of a human pandemic . Influenza viruses that are adapted to transmission in birds and a variety of mammals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses, enabling membrane fusion at comparatively higher pH levels . Here, we combined five mutations in the H5 HA that increased its melting temperature and promoted stable closure of the HA trimer . Structural analysis by cryo–electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions while maintaining the local HA structure . We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than nonstabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative-stain e...