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Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice
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Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice
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Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice
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Journal Article
Baloxavir outperforms oseltamivir, favipiravir, and amantadine in treating lethal influenza A(H5N1) HA clade 2.3.4.4b infection in mice
2026
Overview
Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. Amantadine provided no benefits. Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning.
Here the authors assess baloxavir, oseltamivir, favipiravir, or amantadine for treatment of severe influenza A(H5N1) in female mice and find that baloxavir provides best survival outcomes with reduced lung replication and viral neuroinvasion, supporting its consideration for use in human A(H5N1) infections.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38
/ 38/47
/ 38/77
/ 38/90
/ 38/91
/ 64/60
/ Amantadine - therapeutic use
/ Animals
/ Antiviral Agents - pharmacology
/ Antiviral Agents - therapeutic use
/ Birds
/ Dibenzothiepins - pharmacology
/ Dibenzothiepins - therapeutic use
/ Female
/ Females
/ Humanities and Social Sciences
/ Humans
/ Influenza A Virus, H5N1 Subtype - drug effects
/ Lungs
/ Madin Darby Canine Kidney Cells
/ Mice
/ Orthomyxoviridae Infections - drug therapy
/ Orthomyxoviridae Infections - virology
/ Oseltamivir - therapeutic use
/ Proteins
/ Science
/ Survival
/ Tissues
/ Virus Replication - drug effects
/ Viruses
/ Zoonoses
