7DGI

The co-crystal structure of SARS-CoV-2 main protease with peptidomimetic inhibitor N-((S)-3-methyl-1-(((S)-4-methyl-1-oxo-1-(((S)-1-oxo-3-((S)-2-oxopiperidin-3-yl)propan-2-yl)amino)pentan-2-yl)amino)-1-oxobutan-2-yl)-4-nitrobenzamide

Summary for 7DGI

• Entry DOI: 10.2210/pdb7dgi/pdb
• Descriptor: 3C-like proteinase, ~{N}-[(2~{S})-3-methyl-1-[[(2~{S})-4-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepiperidin-3-yl]propan-2-yl]amino]pentan-2-yl]amino]-1-oxidanylidene-butan-2-yl]-4-nitro-benzamide (3 entities in total)
• Functional Keywords: complex, inhibitor, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 2
• Total formula weight: 68714.30

Authors

Shang, L.Q.,Wang, H. (deposition date: 2020-11-11, release date: 2021-11-24, Last modification date: 2024-10-23)

Primary citation

Wang, H.,Pei, R.,Li, X.,Deng, W.,Xing, S.,Zhang, Y.,Zhang, C.,He, S.,Sun, H.,Xiao, S.,Xiong, J.,Zhang, Y.,Chen, X.,Wang, Y.,Guo, Y.,Zhang, B.,Shang, L.
The structure-based design of peptidomimetic inhibitors against SARS-CoV-2 3C like protease as Potent anti-viral drug candidate.
Eur.J.Med.Chem., 238:114458-114458, 2022

PubMed Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as the pathogen of coronavirus disease 2019 (COVID-19), has infected millions of people and took hundreds of thousands of lives. Unfortunately, there is deficiency of effective medicines to prevent or treat COVID-19. 3C like protease (3CL) of SARS-CoV-2 is essential to the viral replication and transcription, and is an attractive target to develop anti-SARS-CoV-2 agents. Targeting on the 3CL, we screened our protease inhibitor library and obtained compound 10a as hit to weakly inhibit the SARS-CoV-2 3CL, and determined the co-crystal structure of 10a and the protease. Based on the deep understanding on the protein-ligand complexes between the hit and SARS-CoV-2 3CL, we designed a series of peptidomimetic inhibitors, with outstanding inhibitory activity against SARS-CoV-2 3CL and excellent anti-viral potency against SARS-CoV-2. The protein-ligand complexes of the other key inhibitors with SARS-CoV-2 3CL were explicitly described by the X-ray co-crystal study. All such results suggest these peptidomimetic inhibitors could be further applied as encouraging drug candidates.

PubMed: 35635946
DOI: 10.1016/j.ejmech.2022.114458

Experimental method

X-RAY DIFFRACTION (1.898 Å)