Targeting novel structural and functional features of coronavirus protease nsp5 (3CL pro , M pro ) in the age of COVID-19

• Published in: Journal of general virology Vol. 102; no. 3
• Main Authors: Roe, Molly K, Junod, Nathan A, Young, Audrey R, Beachboard, Dia C, Stobart, Christopher C
• Format: Journal Article
• Language: English
• Published: England Microbiology Society 01-03-2021
• Subjects: Amino Acid Sequence; Antiviral Agents - therapeutic use; Coronavirus - enzymology; Coronavirus - metabolism; Coronavirus 3C Proteases - antagonists & inhibitors; Coronavirus 3C Proteases - chemistry; Coronavirus 3C Proteases - genetics; Coronavirus 3C Proteases - metabolism; COVID-19 - virology; COVID-19 Drug Treatment; Humans; Phylogeny; Review; SARS-CoV-2 - enzymology; SARS-CoV-2 - metabolism; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - metabolism; Viral Protease Inhibitors - therapeutic use; protease; inhibitors; nsp5; 3CLpro; Coronavirus
• ISSN: 0022-1317; 1465-2099; 1465-2099
• DOI: 10.1099/JGV.0.001558

Coronavirus protease nsp5 (M
, 3CL
) remains a primary target for coronavirus therapeutics due to its indispensable and conserved role in the proteolytic processing of the viral replicase polyproteins. In this review, we discuss the diversity of known coronaviruses, the role of nsp5 in coronavirus biology, and the structure and function of this protease across the diversity of known coronaviruses, and evaluate past and present efforts to develop inhibitors to the nsp5 protease with a particular emphasis on new and mostly unexplored potential targets of inhibition. With the recent emergence of pandemic SARS-CoV-2, this review provides novel and potentially innovative strategies and directions to develop effective therapeutics against the coronavirus protease nsp5.