8BGA

Structure of Mpro in complex with FGA146

8BGA の概要

• エントリーDOI: 10.2210/pdb8bga/pdb
• 分子名称: 3C-like proteinase nsp5, 4-methoxy-~{N}-[(2~{S})-4-methyl-1-[[(2~{S})-4-nitro-1-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]butan-2-yl]amino]-1-oxidanylidene-pentan-2-yl]-1~{H}-indole-2-carboxamide (3 entities in total)
• 機能のキーワード: mpro, sars-cov-2, fga146, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68626.19

構造登録者

Medrano, F.J.,Romero, A. (登録日: 2022-10-27, 公開日: 2023-11-08, 最終更新日: 2026-03-04)

主引用文献

Medrano, F.J.,de la Hoz-Rodriguez, S.,Marti, S.,Arafet, K.,Schirmeister, T.,Hammerschmidt, S.J.,Muller, C.,Gonzalez-Martinez, A.,Santillana, E.,Ziebuhr, J.,Romero, A.,Zimmer, C.,Weldert, A.,Zimmermann, R.,Lodola, A.,Swiderek, K.,Moliner, V.,Gonzalez, F.V.
Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2.
Commun Chem, 7:15-15, 2024

PubMed Abstract: The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (M) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against M (K: 1-10 μM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC: 1-12 μM) without significant toxicity. Additional kinetic studies of compounds FGA145, FGA146 and FGA147 show that all three compounds inhibit cathepsin L, denoting a possible multitarget effect of these compounds in the antiviral activity. Structural analysis shows the binding mode of FGA146 and FGA147 to the active site of the protein. Furthermore, our results illustrate that peptidyl nitroalkenes are effective covalent reversible inhibitors of the M and cathepsin L, and that inhibitors FGA145, FGA146 and FGA147 prevent infection against SARS-CoV-2.

PubMed: 38238420
DOI: 10.1038/s42004-024-01104-7

実験手法

X-RAY DIFFRACTION (1.982 Å)