6LZE

The crystal structure of COVID-19 main protease in complex with an inhibitor 11a

Summary for 6LZE

• Entry DOI: 10.2210/pdb6lze/pdb
• Related PRD ID: PRD_002347
• Descriptor: 3C-like proteinase, DIMETHYL SULFOXIDE, ~{N}-[(2~{S})-3-cyclohexyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]propan-2-yl]-1~{H}-indole-2-carboxamide, ... (4 entities in total)
• Functional Keywords: protease, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 34214.22

Authors

Zhang, B.,Zhang, Y.,Jing, Z.,Liu, X.,Yang, H.,Liu, H.,Rao, Z.,Jiang, H. (deposition date: 2020-02-19, release date: 2020-04-29, Last modification date: 2024-10-23)

Primary citation

Dai, W.,Zhang, B.,Jiang, X.M.,Su, H.,Li, J.,Zhao, Y.,Xie, X.,Jin, Z.,Peng, J.,Liu, F.,Li, C.,Li, Y.,Bai, F.,Wang, H.,Cheng, X.,Cen, X.,Hu, S.,Yang, X.,Wang, J.,Liu, X.,Xiao, G.,Jiang, H.,Rao, Z.,Zhang, L.K.,Xu, Y.,Yang, H.,Liu, H.
Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.
Science, 368:1331-1335, 2020

PubMed Abstract: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, M, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds ( and ) targeting M Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 M in complex with or , both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of and are covalently bound to cysteine 145 of M Both compounds showed good pharmacokinetic properties in vivo, and also exhibited low toxicity, which suggests that these compounds are promising drug candidates.

PubMed: 32321856
DOI: 10.1126/science.abb4489

Experimental method

X-RAY DIFFRACTION (1.505 Å)