Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.

Mohammad A Ghattas, Noor Atatreh, Radwa E Mahgoub

Journal: Journal of enzyme inhibition and medicinal chemistry 2025;40(1):2460045

PMID: 39912405

Abstract

Peptidomimetic inhibitors mimic natural peptide substrates, employing electrophilic warheads to covalently interact with the catalytic Cys145 of M. Examples include aldehydes, α-ketoamides, and aza-peptides, with discussions on their mechanisms of action, potency, and structural insights. Non-peptidomimetic inhibitors utilise diverse scaffolds and mechanisms, achieving covalent modification of M.

Address: College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates.; AAU Health and Biomedical Research Centre, Al Ain University, Abu Dhabi, United Arab Emirates.

DOI: 10.1080/14756366.2025.2460045

Link outs

Free resources

Full Text Sources:

Miscellaneous:

https://assays.cancer.gov/CPTAC-438

MeSH Terms: Peptidomimetics, SARS-CoV-2, Humans, Coronavirus 3C Proteases, Protease Inhibitors, Antiviral Agents, Structure-Activity Relationship, COVID-19 Drug Treatment