7TE0

Structure of the SARS-CoV-2 main protease in complex with inhibitor PF-07321332

Summary for 7TE0

• Entry DOI: 10.2210/pdb7te0/pdb
• Descriptor: 3C-like proteinase, (1R,2S,5S)-N-{(1E,2S)-1-imino-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}-6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0]hexane-2-carboxamide (3 entities in total)
• Functional Keywords: main protease, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus)
• Total number of polymer chains: 1
• Total formula weight: 34327.09

Authors

Yang, K.S.,Liu, W.R. (deposition date: 2022-01-03, release date: 2022-01-12, Last modification date: 2024-10-30)

Primary citation

Yang, K.S.,Leeuwon, S.Z.,Xu, S.,Liu, W.R.
Evolutionary and Structural Insights about Potential SARS-CoV-2 Evasion of Nirmatrelvir.
J.Med.Chem., 65:8686-8698, 2022

PubMed Abstract: The U.S. FDA approval of PAXLOVID, a combination therapy of nirmatrelvir and ritonavir has significantly boosted our morale in fighting the COVID-19 pandemic. Nirmatrelvir is an inhibitor of the main protease (M) of SARS-CoV-2. Since many SARS-CoV-2 variants that resist vaccines and antibodies have emerged, a concern of acquired viral resistance to nirmatrelvir naturally arises. Here, possible mutations in M to confer viral evasion of nirmatrelvir are analyzed and discussed from both evolutionary and structural standpoints. The analysis indicates that those mutations will likely reside in the whole aa45-51 helical region and residues including M165, L167, P168, R188, and Q189. Relevant mutations have also been observed in existing SARS-CoV-2 samples. Implications of this analysis to the fight against future drug-resistant viral variants and the development of broad-spectrum antivirals are discussed as well.

PubMed: 35731933
DOI: 10.1021/acs.jmedchem.2c00404

Experimental method

X-RAY DIFFRACTION (2 Å)