7MLF

Crystal Structure of SARS-CoV-2 Main Protease (3CLpro/Mpro) Covalently Bound to Compound C7

Summary for 7MLF

• Entry DOI: 10.2210/pdb7mlf/pdb
• Descriptor: 3C-like proteinase, N-(4-tert-butylphenyl)-2-chloro-N-[(1R)-2-(cyclohexylamino)-2-oxo-1-(pyridin-3-yl)ethyl]acetamide (3 entities in total)
• Functional Keywords: sars-cov-2, 3clpro, covalent inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 1
• Total formula weight: 33992.24

Authors

Sharon, I.,Stille, J.,Tjutrins, J.,Wang, G.,Venegas, F.A.,Hennecker, C.,Rueda, A.M.,Miron, C.E.,Pinus, S.,Labarre, A.,Patrascu, M.B.,Vlaho, D.,Huot, M.,Mittermaier, A.K.,Moitessier, N.,Schmeing, T.M. (deposition date: 2021-04-28, release date: 2021-12-22, Last modification date: 2023-10-18)

Primary citation

Stille, J.K.,Tjutrins, J.,Wang, G.,Venegas, F.A.,Hennecker, C.,Rueda, A.M.,Sharon, I.,Blaine, N.,Miron, C.E.,Pinus, S.,Labarre, A.,Plescia, J.,Burai Patrascu, M.,Zhang, X.,Wahba, A.S.,Vlaho, D.,Huot, M.J.,Schmeing, T.M.,Mittermaier, A.K.,Moitessier, N.
Design, synthesis and in vitro evaluation of novel SARS-CoV-2 3CL pro covalent inhibitors.
Eur.J.Med.Chem., 229:114046-114046, 2021

PubMed Abstract: Severe diseases such as the ongoing COVID-19 pandemic, as well as the previous SARS and MERS outbreaks, are the result of coronavirus infections and have demonstrated the urgent need for antiviral drugs to combat these deadly viruses. Due to its essential role in viral replication and function, 3CL (main coronaviruses cysteine-protease) has been identified as a promising target for the development of antiviral drugs. Previously reported SARS-CoV 3CL non-covalent inhibitors were used as a starting point for the development of covalent inhibitors of SARS-CoV-2 3CL. We report herein our efforts in the design and synthesis of submicromolar covalent inhibitors when the enzymatic activity of the viral protease was used as a screening platform.

PubMed: 34995923
DOI: 10.1016/j.ejmech.2021.114046

Experimental method

X-RAY DIFFRACTION (2.6 Å)