SARS-CoV-2 Papain-like ProteaseTargeted Library

SARS-CoV-2 Papain-like Protease (PLpro) Targeted Library contains 1058 compounds with predicted activity against this protease. The library has been designed with receptor-based virtual screening using crystal structure (PDB ID: 6W9C) of SARS-CoV-2 PLpro. The SARS-CoV-2 papain-like protease (PLpro) is a part of NSP3 multi-domain protein. It is essential for coronaviral replication. PLpro has also the additional function - stripping ubiquitin and ISG15 from host-cell proteins to aid coronaviruses in their evasion of the host innate immune responses. Thereby this enzyme is an attractive antiviral drug target.
The overall procedure included accurate flexible docking of Drug-like Green Collection into protease cleavage site. Final selection of compounds was made with inspection of enzyme active site’s crucial structural determinants for ligand binding, docking scores and intermolecular hydrogen bonds with key active site’s amino acid residues, including classic catalytic triad, composed of Cys111–His272–Asp286, that located at the interface of the thumb and palm sub-domains.