Broad Spectrum Inhibitor of Influenza A and B Viruses Targeting the Viral Nucleoprotein.

ABSTRACT: S119 was a top hit from an ultrahigh throughput screen performed to identify novel inhibitors of influenza virus replication. It showed a potent antiviral effect (50% inhibitory concentration, IC₅₀ = 20 nM) and no detectable cytotoxicity (50% cytotoxic concentration, CC₅₀ > 500 μM) to yield a selectivity index greater than 25 000. Upon investigation, we found that S119 selected for resistant viruses carrying mutations in the viral nucleoprotein (NP). These resistance mutations highlight a likely S119 binding site overlapping with but not identical to that found for the compound nucleozin. Mechanism of action studies revealed that S119 affects both the oligomerization state and cellular localization of the NP protein which has an impact on viral transcription, replicat

SUBMITTER: White KM 

PROVIDER: S-EPMC6145453 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature