Publication date: Dec 18, 2025
The cysteine 3C-like proteases (3CL) of caliciviruses, coronaviruses, and picornaviruses are essential for viral replication. In this study, we report the development of potent broad-spectrum peptidomimetic antiviral agents that target the 3CL of caliciviruses (NS6), coronaviruses (M), and a picornavirus (3C). Based upon previously reported inhibitors, a small library of compounds was designed, synthesized and tested to identify a core structure, which was then derivatized with a focus upon P3 and P4 positions to afford new inhibitors with improved potency against the respective viral enzymes and enhanced binding as determined by X-ray crystallography. These compounds were tested against a range of viruses in culture, revealing minimal toxicity while exhibiting broad-spectrum potent nanomolar activities against noroviruses and several coronavirus species, including alpha and omicron variants of SARS-CoV-2 and Middle East Respiratory Syndrome virus (MERS).
Semantics
| Type | Source | Name |
|---|---|---|
| drug | DRUGBANK | L-Cysteine |
| pathway | KEGG | Viral replication |
| disease | MESH | NS6 |
| disease | MESH | Middle East Respiratory Syndrome |