7RNW

SARS-CoV-2 Main Protease in complex with a cyclic peptide inhibitor

7RNW の概要

• エントリーDOI: 10.2210/pdb7rnw/pdb
• 分子名称: 3C-like proteinase, ACE-DTY-LEU-GLN-TYR-ALA-VAL-LEU-ARG-HIS-LYS-ARG-ARG-GLU-SEC (3 entities in total)
• 機能のキーワード: protease, drug design, complex, 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, SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 142950.70

構造登録者

Frkic, R.L.,Jackson, C.J. (登録日: 2021-07-30, 公開日: 2022-03-16, 最終更新日: 2023-10-18)

主引用文献

Johansen-Leete, J.,Ullrich, S.,Fry, S.E.,Frkic, R.,Bedding, M.J.,Aggarwal, A.,Ashhurst, A.S.,Ekanayake, K.B.,Mahawaththa, M.C.,Sasi, V.M.,Luedtke, S.,Ford, D.J.,O'Donoghue, A.J.,Passioura, T.,Larance, M.,Otting, G.,Turville, S.,Jackson, C.J.,Nitsche, C.,Payne, R.J.
Antiviral cyclic peptides targeting the main protease of SARS-CoV-2.
Chem Sci, 13:3826-3836, 2022

PubMed Abstract: Antivirals that specifically target SARS-CoV-2 are needed to control the COVID-19 pandemic. The main protease (M) is essential for SARS-CoV-2 replication and is an attractive target for antiviral development. Here we report the use of the Random nonstandard Peptide Integrated Discovery (RaPID) mRNA display on a chemically cross-linked SARS-CoV-2 M dimer, which yielded several high-affinity thioether-linked cyclic peptide inhibitors of the protease. Structural analysis of M complexed with a selenoether analogue of the highest-affinity peptide revealed key binding interactions, including glutamine and leucine residues in sites S1 and S2, respectively, and a binding epitope straddling both protein chains in the physiological dimer. Several of these M peptide inhibitors possessed antiviral activity against SARS-CoV-2 with EC values in the low micromolar range. These cyclic peptides serve as a foundation for the development of much needed antivirals that specifically target SARS-CoV-2.

PubMed: 35432913
DOI: 10.1039/d1sc06750h

実験手法

X-RAY DIFFRACTION (2.35 Å)