7K6D

SARS-CoV-2 Main Protease Co-Crystal Structure with Telaprevir Determined from Crystals Grown with 40 nL Acoustically Ejected Mpro Droplets at 1.48 A Resolution (Cryo-protected)

7K6D の概要

• エントリーDOI: 10.2210/pdb7k6d/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002448
• 分子名称: 3C-like proteinase, DIMETHYL SULFOXIDE, (1S,3aR,6aS)-2-[(2S)-2-({(2S)-2-cyclohexyl-2-[(pyrazin-2-ylcarbonyl)amino]acetyl}amino)-3,3-dimethylbutanoyl]-N-[(2R,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl]octahydrocyclopenta[c]pyrrole-1-carboxamide, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, main protease, 3clpro/mpro, telaprevir, viral protein, acoustic drop ejection, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34585.54

構造登録者

Kreitler, D.F.,Andi, B.,Kumaran, D.,Soares, A.S.,Shi, W.,Jakoncic, J.,Fuchs, M.R.,Keereetaweep, J.,Shanklin, J.,McSweeney, S. (登録日: 2020-09-19, 公開日: 2020-09-30, 最終更新日: 2024-10-09)

主引用文献

Andi, B.,Kumaran, D.,Kreitler, D.F.,Soares, A.S.,Keereetaweep, J.,Jakoncic, J.,Lazo, E.O.,Shi, W.,Fuchs, M.R.,Sweet, R.M.,Shanklin, J.,Adams, P.D.,Schmidt, J.G.,Head, M.S.,McSweeney, S.
Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease.
Sci Rep, 12:12197-12197, 2022

PubMed Abstract: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (M also known as 3CL) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the M Cys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the M as potential COVID-19 therapeutics for further testing and possibly clinical trials.

PubMed: 35842458
DOI: 10.1038/s41598-022-15930-z

実験手法

X-RAY DIFFRACTION (1.48 Å)