Baloxavir and molnupiravir protect against severe A/H5N1 infection in immunosuppressed hamsters

Baloxavir and molnupiravir protect against severe A/H5N1 infection in immunosuppressed hamsters | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Brief Communication Baloxavir and molnupiravir protect against severe A/H5N1 infection in immunosuppressed hamsters Mariana Baz, Andrea Arroyave, Henintsoa Rabezanahary, Ahmed Sahli This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9193430/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Highly pathogenic avian influenza A/H5N1 viruses continue to spread among multiple mammalian species, including humans, raising concerns about zoonotic transmission and pandemic preparedness. Immunocompromised individuals often develop severe and prolonged disease, yet evidence guiding antiviral therapy in these patients remains limited. We investigated pathogenesis, transmissibility, and antiviral efficacy of oseltamivir, baloxavir, and molnupiravir against a human A/H5N1 clade 2.3.4.4b genotype D1.1 virus isolated in Canada using a cyclophosphamide-immunosuppressed hamster model. A/H5N1 infection caused severe disease in immunosuppressed hamsters with no contact transmission. Baloxavir conferred complete survival, markedly reduced viral burden, and prevented neuroinvasion, while high-dose molnupiravir and combination therapy with oseltamivir and low-dose molnupiravir improved outcomes and achieved viral clearance in lung and brain tissues. These findings support baloxavir as an effective therapeutic option for severe A/H5N1 infection in immunocompromised hosts and identify molnupiravir as a promising antiviral candidate, with implications for pandemic preparedness strategies targeting vulnerable populations. Biological sciences/Microbiology/Virology/Influenza virus Health sciences/Diseases/Infectious diseases/Influenza virus Health sciences/Medical research/Preclinical research Full Text Additional Declarations There is NO Competing Interest. Supplementary Files ExtendedDataTableArroyaveatal.2026.xlsx Extended Data Table 1. Clinical signs, tissue viral titers and antiviral resistance profiling in A/H5N1-infected IS hamsters. Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9193430","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Brief Communication","associatedPublications":[],"authors":[{"id":611510973,"identity":"be1df7e6-746c-447f-a678-08944ef73cad","order_by":0,"name":"Mariana Baz","email":"data:image/png;base64,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","orcid":"","institution":"Université Laval","correspondingAuthor":true,"prefix":"","firstName":"Mariana","middleName":"","lastName":"Baz","suffix":""},{"id":611510974,"identity":"d098ec39-ea19-4a56-8e92-0b93727049af","order_by":1,"name":"Andrea Arroyave","email":"","orcid":"https://orcid.org/0009-0007-0518-213X","institution":"Université Laval","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Arroyave","suffix":""},{"id":611510975,"identity":"ea84acc2-d189-4653-b938-e4e10d1b030b","order_by":2,"name":"Henintsoa Rabezanahary","email":"","orcid":"","institution":"Université Laval","correspondingAuthor":false,"prefix":"","firstName":"Henintsoa","middleName":"","lastName":"Rabezanahary","suffix":""},{"id":611510976,"identity":"30bf0c85-a64b-41dc-90eb-f1262197c15f","order_by":3,"name":"Ahmed Sahli","email":"","orcid":"https://orcid.org/0009-0003-5103-3777","institution":"Université Laval","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Sahli","suffix":""}],"badges":[],"createdAt":"2026-03-22 19:50:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9193430/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9193430/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106094117,"identity":"4bdf14cb-ebb1-4bef-a7c5-affc9f87f5cc","added_by":"auto","created_at":"2026-04-03 11:41:07","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2955022,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Arroyaveetal.H5N1antivirals2026.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9193430/v1_covered_3cde2992-71c9-48bb-9c1d-664806fb1267.pdf"},{"id":105970105,"identity":"517982b2-adc2-420b-affc-6a5c0f807813","added_by":"auto","created_at":"2026-04-02 03:18:03","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19275,"visible":true,"origin":"","legend":"Extended Data Table 1. 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