Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus.

ABSTRACT: The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to

SUBMITTER: Tarus B 

PROVIDER: S-EPMC4548311 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature