8DZC

Crystal structure of the SARS-CoV-2 (COVID-19) main protease in complex with inhibitor 17

8DZC の概要

• エントリーDOI: 10.2210/pdb8dzc/pdb
• 分子名称: 3C-like proteinase nsp5, (3,5-difluorophenyl)methyl {(3S)-1-[(2S)-1-({(2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-6-oxopiperidin-3-yl}carbamate, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: covid, covid19, covid-19, sars, sars cov2, cov, ncov 19, coronavirus, main protease, 3cl, mpro, pro, gc376, calpain inhibitor ii, leupeptin, calpain, aldehyde, gc-376, 3cl-like, a-ketoamide, alpheketoamide, alpha, ketoamide, petidometic, protease, cysteine, hydrolase-hydrolase inhibitor complex, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34539.31

構造登録者

Sacco, M.,Chen, Y. (登録日: 2022-08-06, 公開日: 2023-04-05, 最終更新日: 2024-10-30)

主引用文献

Wang, L.,Ma, C.,Sacco, M.D.,Xue, S.,Mahmoud, M.,Calcul, L.,Chen, Y.,Wang, J.,Cai, J.
Development of the Safe and Broad-Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained alpha , gamma-AA Peptide Scaffold.
Chemistry, 29:e202300476-e202300476, 2023

PubMed Abstract: SARS-CoV-2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (M ) is essential in the replication of SARS-CoV-2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics-constrained α, γ-AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the M of SARS-CoV-2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET-based M enzymatic assay not only for the M of SARS-CoV-2 but also for SARS-CoV and MERS-CoV, along with HCoVs like HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. The X-ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS-CoV-2. Overall, the results suggest that α, γ-AA peptide could be a promising molecular scaffold in designing novel M inhibitors of SARS-CoV-2 and other coronaviruses.

PubMed: 36920943
DOI: 10.1002/chem.202300476

実験手法

X-RAY DIFFRACTION (2.2 Å)