9PFH

Crystal structure of SARS-CoV-2 Mpro Mutant P132H with C5a

Summary for 9PFH

• Entry DOI: 10.2210/pdb9pfh/pdb
• Descriptor: 3C-like proteinase nsp5, N-[(4-chlorothiophen-2-yl)methyl]-N-[4-(dimethylamino)phenyl]-2-(5-hydroxyisoquinolin-4-yl)acetamide (3 entities in total)
• Functional Keywords: mutant, inhibitor, viral protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 2
• Total formula weight: 68637.09

Authors

Kenward, C.,Mosimann, W.A.,Worrall, L.J.,Strynadka, N.C.J. (deposition date: 2025-07-04, release date: 2025-07-16)

Primary citation

Deschenes, N.M.,Perez-Vargas, J.,Zhong, Z.,Thomas, M.,Kenward, C.,Mosimann, W.A.,Worrall, L.J.,Waglechner, N.,Li, A.X.,Maguire, F.,Aftanas, P.,Smith, J.R.,Lim, J.,Young, R.N.,Cherkasov, A.,Farooqi, L.,Moinuddin, A.,Siddiqi, L.,Malik, I.,Lefebvre, M.,Paetzel, M.,Strynadka, N.C.J.,Jean, F.,McGeer, A.,Kozak, R.A.
Functional and structural characterization of treatment-emergent nirmatrelvir resistance mutations at low frequencies in the main protease (Mpro) reveals a unique evolutionary route for SARS-CoV-2 to gain resistance.
J Infect Dis, 2025

PubMed Abstract: The main protease (Mpro) is one of the most attractive targets for antiviral drug discovery against SARS-CoV-2. Mutations in Mpro have been linked to resistance against nirmatrelvir-ritonavir (NIR-RIT), an important therapy for SARS-CoV-2 infection. This study aimed to identify low-frequency antiviral resistance mutations in Mpro from NIR-RIT-treated patients and to analyze the enzymatic properties, inhibitor susceptibility, and structural features of new Mpro clinical variants.

PubMed: 40459233
DOI: 10.1093/infdis/jiaf294

Experimental method

X-RAY DIFFRACTION (2.69 Å)