6Y7M

Crystal structure of the complex resulting from the reaction between the SARS-CoV main protease and tert-butyl (1-((S)-3-cyclohexyl-1-(((S)-4-(cyclopropylamino)-3,4-dioxo-1-((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-1-oxopropan-2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate

これはPDB形式変換不可エントリーです。

6Y7M の概要

• エントリーDOI: 10.2210/pdb6y7m/pdb
• 分子名称: 3C-like proteinase, ~{tert}-butyl ~{N}-[1-[(2~{S})-3-cyclohexyl-1-[[(2~{S},3~{R})-4-(cyclopropylamino)-3-oxidanyl-4-oxidanylidene-1-[(3~{R})-2-oxidanylidene-3,4-dihydropyrrol-3-yl]butan-2-yl]amino]-1-oxidanylidene-propan-2-yl]-2-oxidanylidene-pyridin-3-yl]carbamate, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: coronavirus, alpha-ketoamide, antiviral, drug design, viral protease, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus (SARS-CoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34540.46

構造登録者

Zhang, L.,Lin, D.,Hilgenfeld, R. (登録日: 2020-03-01, 公開日: 2020-03-18, 最終更新日: 2024-10-23)

主引用文献

Zhang, L.,Lin, D.,Sun, X.,Curth, U.,Drosten, C.,Sauerhering, L.,Becker, S.,Rox, K.,Hilgenfeld, R.
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved alpha-ketoamide inhibitors.
Science, 368:409-412, 2020

PubMed Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (M, also called 3CL) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 M and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.

PubMed: 32198291
DOI: 10.1126/science.abb3405

実験手法

X-RAY DIFFRACTION (1.9 Å)