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Emerg Microbes Infect . Antiviral activities of multiple antivirals against highly pathogenic avian influenza A H5N1 in vitro and in mice

tetano

Editor, Senior Moderator
Emerg Microbes Infect


. 2026 Dec;15(1):2645843.
doi: 10.1080/22221751.2026.2645843. Epub 2026 Mar 31.
Antiviral activities of multiple antivirals against highly pathogenic avian influenza A H5N1 in vitro and in mice

Danlei Liu[SUP] 1 [/SUP], Yujing Fan[SUP] 1 [/SUP], Ka-Yi Leung[SUP] 1 [/SUP], Ruiqi Zhang[SUP] 1 [/SUP], Hoi-Yan Lam[SUP] 2 [/SUP], Xiaochun Xie[SUP] 1 [/SUP], Honglin Chen[SUP] 2 3 4 5 [/SUP], Kwok-Hung Chan[SUP] 2 3 4 5 [/SUP], Ivan Fan-Ngai Hung[SUP] 1 3 4 [/SUP]


Affiliations
Abstract

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC[SUB]50[/SUB] of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD[SUB]50[/SUB]) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Keywords: H5N1; Highly pathogenic avian influenza; antiviral treatment; dairy cow; mouse model.

 
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