7C6S

Crystal structure of the SARS-CoV-2 main protease complexed with Boceprevir

7C6S の概要

• エントリーDOI: 10.2210/pdb7c6s/pdb
• 分子名称: 3C-like proteinase, boceprevir (bound form) (3 entities in total)
• 機能のキーワード: sars-cov-2, main protease, inhibitor, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34347.24

構造登録者

Fu, L.,Feng, Y. (登録日: 2020-05-22, 公開日: 2020-09-02, 最終更新日: 2024-10-09)

主引用文献

Fu, L.,Ye, F.,Feng, Y.,Yu, F.,Wang, Q.,Wu, Y.,Zhao, C.,Sun, H.,Huang, B.,Niu, P.,Song, H.,Shi, Y.,Li, X.,Tan, W.,Qi, J.,Gao, G.F.
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease.
Nat Commun, 11:4417-4417, 2020

PubMed Abstract: COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M, also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting M. Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease M as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.

PubMed: 32887884
DOI: 10.1038/s41467-020-18233-x

実験手法

X-RAY DIFFRACTION (1.6 Å)