Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir.

ABSTRACT: Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting the cap-binding function of polymerase basic protein 2 (PB2). In this study, we used a combination of sequence analysis and phenotypic methods to evaluate pimodivir susceptibility of influenza A viruses collected from humans and other hosts. Screening PB2 sequences for substitutions previously associated with reduced pimodivir susceptibility revealed a very low frequency among seasonal viruses circulating in the U.S. during 2015-2020 (<0.03%; 3/11,934) and among non-seasonal viruses collected in various countries during the same period (0.2%; 18/8971). Pimodivir potently inhibited virus replication in two assays, a single-cycle HINT and a multi-cycle FRA, with IC₅₀ values in a

SUBMITTER: Patel MC 

PROVIDER: S-EPMC8978222 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature