Targeting SARS-CoV-2 nonstructural protein 3: function, structure, inhibition, and perspective in drug discovery

Drug Discov Today. 2023 Nov 15:103832. doi: 10.1016/j.drudis.2023.103832. Online ahead of print.ABSTRACTAs a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we provide a comprehensive review of the function, structure, and inhibition of SARS-CoV/-CoV-2 PLpro and Mac1. We also discuss advances in, and challenges to, the discovery of drugs against these targets.PMID:37977285 | DOI:10.1016/j.drudis.2023.103832
Source: Drug Discovery Today - Category: Drugs & Pharmacology Authors: Source Type: research