6XMK

1.70 A resolution structure of SARS-CoV-2 3CL protease in complex with inhibitor 7j

6XMK の概要

• エントリーDOI: 10.2210/pdb6xmk/pdb
• 分子名称: 3C-like proteinase, (1S,2S)-2-[(N-{[(4,4-difluorocyclohexyl)methoxy]carbonyl}-L-leucyl)amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: protease, severe acute respiratory syndrome coronavirus 2, sars-cov-2 3cl protease inhhibitors, covid-19, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 2
• 化学式量合計: 69387.00

構造登録者

Lovell, S.,Kashipathy, M.M.,Battaile, K.P.,Rathnayake, A.D.,Zheng, J.,Kim, Y.,Nguyen, H.N.,Chang, K.O.,Groutas, W.C. (登録日: 2020-06-30, 公開日: 2020-07-08, 最終更新日: 2023-10-18)

主引用文献

Rathnayake, A.D.,Zheng, J.,Kim, Y.,Perera, K.D.,Mackin, S.,Meyerholz, D.K.,Kashipathy, M.M.,Battaile, K.P.,Lovell, S.,Perlman, S.,Groutas, W.C.,Chang, K.O.
3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice.
Sci Transl Med, 12:-, 2020

PubMed Abstract: Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.

PubMed: 32747425
DOI: 10.1126/scitranslmed.abc5332

実験手法

X-RAY DIFFRACTION (1.7 Å)