Structure-based virtual screening against SARS-3CL ^pro to identify novel non-peptidic hits

Graphical abstract

Novel inhibitors of the SARS-3CL ^pro were identified using a combination of structure-based virtual screening and biological evaluation.

Abstract

Severe acute respiratory syndrome is a highly infectious upper respiratory tract disease caused by SARS-CoV, a previously unidentified human coronavirus. SARS-3CL ^pro is a viral cysteine protease critical to the pathogen’s life cycle and hence a therapeutic target of importance. The recently elucidated crystal structures of this enzyme provide an opportunity for the discovery of inhibitors through rational drug design. In the current study, Gold docking program was utilized to conduct extensive docking studies against the target crystal structure to develop a robust and predictive docking protocol. The validated docking protocol was used to conduct a structure-based virtual screening of the Asinex Platinum collection. Biological evaluation of a screened selection of compounds was carried out to identify novel inhibitors of the viral protease.