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

Abstract

Peptidomimetic inhibitors mimic natural peptide substrates, employing electrophilic warheads to covalently interact with the catalytic Cys145 of Mpro. 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 Mpro.