Journal article

Novel inhibitors targeting Venezuelan equine encephalitis virus capsid protein identified using In Silico Structure-Based-Drug-Design

Sharon Shechter, David R Thomas, Lindsay Lundberg, Chelsea Pinkham, Shih-Chao Lin, Kylie M Wagstaff, Aaron Debono, Kylene Kehn-Hall, David A Jans

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2017

Abstract

Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1.5 million compounds, followed by in silico refinement and screening for biological activity in vitro, we identified 21 hit compounds which inhibited IMPα/β1:C binding with IC50s as low as 5 µM. Four compounds were fou..

View full abstract

University of Melbourne Researchers