7V7M

crystal structure of SARS-CoV-2 3CL protease

7V7M の概要

• エントリーDOI: 10.2210/pdb7v7m/pdb
• 分子名称: 3C-like proteinase (2 entities in total)
• 機能のキーワード: protease, 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: 33825.55

構造登録者

Yi, Y.,Zhang, M.,Ye, M. (登録日: 2021-08-21, 公開日: 2022-06-29, 最終更新日: 2024-01-17)

主引用文献

Yi, Y.,Zhang, M.,Xue, H.,Yu, R.,Bao, Y.O.,Kuang, Y.,Chai, Y.,Ma, W.,Wang, J.,Shi, X.,Li, W.,Hong, W.,Li, J.,Muturi, E.,Wei, H.,Wlodarz, J.,Roszak, S.,Qiao, X.,Yang, H.,Ye, M.
Schaftoside inhibits 3CL pro and PL pro of SARS-CoV-2 virus and regulates immune response and inflammation of host cells for the treatment of COVID-19.
Acta Pharm Sin B, 12:4154-4164, 2022

PubMed Abstract: It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL) and papain-like protease (PL) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL and PL with IC values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL, and K157, E167 and A246 of PL. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

PubMed: 35968270
DOI: 10.1016/j.apsb.2022.07.017

実験手法

X-RAY DIFFRACTION (2.08 Å)