6XCH

Room-temperature X-ray Crystal structure of SARS-CoV-2 main protease in complex with Leupeptin

6XCH の概要

• エントリーDOI: 10.2210/pdb6xch/pdb
• 分子名称: 3C-like proteinase, Leupeptin (3 entities in total)
• 機能のキーワード: sars-cov-2 main protease, viral protein, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34255.13

構造登録者

Kneller, D.W.,Kovalevsky, A.,Coates, L. (登録日: 2020-06-08, 公開日: 2020-06-17, 最終更新日: 2024-11-13)

主引用文献

Kneller, D.W.,Galanie, S.,Phillips, G.,O'Neill, H.M.,Coates, L.,Kovalevsky, A.
Malleability of the SARS-CoV-2 3CL M pro Active-Site Cavity Facilitates Binding of Clinical Antivirals.
Structure, 28:1313-, 2020

PubMed Abstract: The COVID-19 pandemic caused by SARS-CoV-2 requires rapid development of specific therapeutics and vaccines. The main protease of SARS-CoV-2, 3CL M, is an established drug target for the design of inhibitors to stop the virus replication. Repurposing existing clinical drugs can offer a faster route to treatments. Here, we report on the binding mode and inhibition properties of several inhibitors using room temperature X-ray crystallography and in vitro enzyme kinetics. The enzyme active-site cavity reveals a high degree of malleability, allowing aldehyde leupeptin and hepatitis C clinical protease inhibitors (telaprevir, narlaprevir, and boceprevir) to bind and inhibit SARS-CoV-2 3CL M. Narlaprevir, boceprevir, and telaprevir are low-micromolar inhibitors, whereas the binding affinity of leupeptin is substantially weaker. Repurposing hepatitis C clinical drugs as COVID-19 treatments may be a useful option to pursue. The observed malleability of the enzyme active-site cavity should be considered for the successful design of specific protease inhibitors.

PubMed: 33152262
DOI: 10.1016/j.str.2020.10.007

実験手法

X-RAY DIFFRACTION (2.2 Å)