A Potent Anti-influenza Compound Blocks Fusion through Stabilization of the Prefusion Conformation of the Hemagglutinin Protein.

ABSTRACT: An ultrahigh-throughput screen was performed to identify novel small molecule inhibitors of influenza virus replication. The screen employed a recombinant influenza A/WSN/33 virus expressing Renilla luciferase and yielded a hit rate of 0.5%, of which the vast majority showed little cytotoxicity at the inhibitory concentration. One of the top hits from this screen, designated S20, inhibits HA-mediated membrane fusion. S20 shows potent antiviral activity (IC₅₀ = 80 nM) and low toxicity (CC₅₀ = 40 μM), yielding a selectivity index of 500 and functionality against all of the group 1 influenza A viruses tested in this study, including the pandemic H1N1 and avian H5N1 viruses. Mechanism of action studies proved a direct S20-HA interaction and showed that S20 inhibits

SUBMITTER: White KM 

PROVIDER: S-EPMC4426349 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature