3C-like protease

The Enzyme Commission refers to this family as SARS coronavirus main proteinase (Mpro; EC 3.4.22.69).

A number of protease inhibitors are being developed targeting 3CLpro and homologous 3Cpro, including CLpro-1, GC376, rupintrivir, lufotrelvir, PF-07321332, and AG7404.

[15] After clinical trials, in December 2021, the oral medication nirmatrelvir (formerly PF-07321332) became commercially available under emergency use authorizations (EUA), as part of the nirmatrelvir/ritonavir combination therapy (brand name Paxlovid).

[19][20] In 2022, an ultralarge virtual screening campaign of 235 million molecules was able to identify a novel broad-spectrum inhibitor targeting the main protease of several coronaviruses.

They are divided into subfamilies by sequence similarity, corresponding to the family of viruses they are found in:[22] Additional members are known from Potyviridae and non-Coronaviridae Nidovirales.

Nirmatrelvir bound to 3CL PDB : 7RFW ​
Nirmatrelvir , a 3CLpro inhibitor developed by Pfizer in phase II/III clinical trials as a combination drug with ritonavir . [ 9 ] [ 10 ]
A ligand-binding diagram showing the amino acid residues in contact with a covalently bound peptidomimetic protease inhibitor . The small red spheres are water molecules . [ 1 ]