A novel, covalent broad-spectrum inhibitor targeting human coronavirus Mpro DOI Creative Commons
Jing Sun,

Deheng Sun,

Qi Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 15, 2025

Human coronaviruses (CoV) cause respiratory infections that range from mild to severe. CoVs are a large family of viruses with considerable genetic heterogeneity and multitude viral types, making preventing treating these difficult. Comprehensive treatments inhibit CoV fulfill pressing medical need may be immensely valuable in managing emerging endemic infections. As the main protease (Mpro) is highly conserved across many CoVs, this has been identified as route for broad inhibition. We utilize advanced generative chemistry platform Chemistry42 de novo molecular design obtained novel small-molecule, non-peptide-like inhibitors targeting SARS-CoV-2 Mpro. ISM3312 an irreversible, covalent Mpro inhibitor extensive virtual screening structure-based optimization efforts. exhibits low off-target risk outstanding antiviral activity against multiple human coronaviruses, including SARS-CoV-2, MERS-CoV, 229E, OC43, NL63, HKU1 independent P-glycoprotein (P-gp) Furthermore, shows significant inhibitory effects Nirmatrelvir-resistant mutants, suggesting contribute reduced escape settings. Incorporating Nirmatrelvir into strategy could improve preparedness reinforce defenses future coronavirus threats.

Language: Английский

Enhancing the understandings on SARS-CoV-2 main protease (Mpro) mutants from molecular dynamics and machine learning DOI
Jiawen Wang, Juan Xie,

Yi Yu

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143076 - 143076

Published: April 1, 2025

Language: Английский

Citations

0
A novel, covalent broad-spectrum inhibitor targeting human coronavirus Mpro DOI Creative Commons
Jing Sun,

Deheng Sun,

Qi Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 15, 2025

Human coronaviruses (CoV) cause respiratory infections that range from mild to severe. CoVs are a large family of viruses with considerable genetic heterogeneity and multitude viral types, making preventing treating these difficult. Comprehensive treatments inhibit CoV fulfill pressing medical need may be immensely valuable in managing emerging endemic infections. As the main protease (Mpro) is highly conserved across many CoVs, this has been identified as route for broad inhibition. We utilize advanced generative chemistry platform Chemistry42 de novo molecular design obtained novel small-molecule, non-peptide-like inhibitors targeting SARS-CoV-2 Mpro. ISM3312 an irreversible, covalent Mpro inhibitor extensive virtual screening structure-based optimization efforts. exhibits low off-target risk outstanding antiviral activity against multiple human coronaviruses, including SARS-CoV-2, MERS-CoV, 229E, OC43, NL63, HKU1 independent P-glycoprotein (P-gp) Furthermore, shows significant inhibitory effects Nirmatrelvir-resistant mutants, suggesting contribute reduced escape settings. Incorporating Nirmatrelvir into strategy could improve preparedness reinforce defenses future coronavirus threats.

Language: Английский

Citations

0