Abstract
Viral neuraminidase inhibitors show limited efficacy in mice infected with H7N9 influenza A viruses isolated from humans. Although baloxavir marboxil protected mice from lethal challenge infection with a low pathogenic avian influenza H7N9 virus isolated from a human, its efficacy in mice infected with a recent highly pathogenic version of H7N9 human isolates is unknown. Here, we examined the efficacy of baloxavir marboxil in mice infected with a highly pathogenic human H7N9 virus, A/Guangdong/17SF003/2016. Treatment of infected mice with a single 1.5 mg/kg dose of baloxavir marboxil protected mice from the highly pathogenic human H7N9 virus infection as effectively as oseltamivir treatment at 50 mg/kg twice a day for five days. Daily treatment for five days at 15 or 50 mg/kg of baloxavir marboxil showed superior therapeutic efficacy, largely preventing virus replication in respiratory organs. These results indicate that baloxavir marboxil is a valuable candidate treatment for human patients suffering from highly pathogenic H7N9 virus infection.
Highlights
Treatment of zoonotic influenza with neuraminidase (NA) inhibitors that target the viral sialidase activity of NA is thought to be effective
In patients infected with a seasonal influenza virus, baloxavir treatment reduced the viral load after only 1 day of treatment, which is more rapid than treatment with an NA inhibitor; the time to symptom improvement was similar between baloxavir marboxil and NA inhibitor treatments [3]
To evaluate the efficacy of baloxavir marboxil in vivo infection with the H7N9 virus, baloxavir marboxil was orally administered to mice at 5 and 50 mg/kg twice a day for five days and was shown marboxil was orally administered to mice at 5 and 50 mg/kg twice a day for five days and was shown to have completely protected them from lethal challenge infection with a low pathogenic avian H7N9 to have completely protected them from lethal challenge infection with a low pathogenic avian H7N9 human isolate, A/Anhui/1/2013 [18]
Summary
Treatment of zoonotic influenza with neuraminidase (NA) inhibitors that target the viral sialidase activity of NA is thought to be effective. Efficacy of baloxavir marboxil against this highly pathogenic human H7N9 virus in vitro and in vivo. We assessed the efficacy of baloxavir marboxil in mice infected with the highly pathogenic
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