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The COVID-19 pandemic has served as a stark reminder that outbreaks of novel pathogens (i.e., those not previously encountered by humans) have always plagued mankind and will continue to do so. The COVID-19 pandemic has also taught us that a single exposure to a novel pathogen is typically not sufficient to build robust population immunity that exists against common respiratory viruses. Robust population-level immunity can be achieved through repeated natural infection (typically at the cost of high mortality and overwhelmed public health resources) and/or repeated vaccination (which may be limited by vaccine availability, a country's economic resources, and/or vaccine hesitancy). Here, we suggest that the broader use of antivirals could be a mitigation strategy to limit severe disease and the burden on healthcare systems during widespread virus circulation while allowing the buildup of population immunity.

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.

Routine surveillance in live poultry markets in the northern regions of Vietnam from 2016 to 2017 resulted in the isolation of 27 highly pathogenic avian H5N1 and H5N6 viruses of 3 different clades (2.3.2.1c, 2.3.4.4f, and 2.3.4.4g). Sequence and phylogenetic analysis of these viruses revealed reassortment with various subtypes of low pathogenic avian influenza viruses. Deep-sequencing identified minor viral subpopulations encoding variants that may affect pathogenicity and sensitivity to antiviral drugs. Interestingly, mice infected with two different clade 2.3.2.1c viruses lost body weight rapidly and succumbed to virus infection, whereas mice infected with clade 2.3.4.4f or 2.3.4.4g viruses experienced non-lethal infections. [ABSTRACT FROM AUTHOR]