Hemagglutinin Stability Determines Influenza A Virus Susceptibility to a Broad-Spectrum Fusion Inhibitor Arbidol.

ABSTRACT: Understanding mechanisms of resistance to antiviral inhibitors can reveal nuanced features of targeted viral mechanisms and, in turn, lead to improved strategies for inhibitor design. Arbidol is a broad-spectrum antiviral that binds to and prevents the fusion-associated conformational changes in the trimeric influenza A virus (IAV) hemagglutinin (HA). The rate-limiting step during the HA-mediated membrane fusion is the release of the hydrophobic fusion peptides from a conserved pocket on HA. Here, we investigated how destabilizing or stabilizing mutations in or near the fusion peptide affect viral sensitivity to Arbidol. The degree of sensitivity was proportional to the extent of fusion-peptide stability on the prefusion HA: stabilized mutants were more sensitive, and destabilized ones wer

SUBMITTER: Li Z 

PROVIDER: S-EPMC9810120 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature