In silico screening for human norovirus antivirals reveals a novel non-nucleoside inhibitor of the viral polymerase.

ABSTRACT: Human norovirus causes approximately 219,000 deaths annually, yet there are currently no antivirals available. A virtual screening of commercially available drug-like compounds (~300,000) was performed on the suramin and PPNDS binding-sites of the norovirus RNA-dependent RNA polymerase (RdRp). Selected compounds (n = 62) were examined for inhibition of norovirus RdRp activity using an in vitro transcription assay. Eight candidates demonstrated RdRp inhibition (>25% inhibition at 10 µM), which was confirmed using a gel-shift RdRp assay for two of them. The two molecules were identified as initial hits and selected for structure-activity relationship studies, which resulted in the synthesis of novel compounds that were examined for inhibitory activity. Five compounds inhibited human noroviru

SUBMITTER: Ferla S 

PROVIDER: S-EPMC5841303 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature