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7T49

Structure of SARS-CoV-2 3CL protease in complex with inhibitor 10c

Summary for 7T49
Entry DOI10.2210/pdb7t49/pdb
Descriptor3C-like proteinase, (1R,2S)-1-hydroxy-2-{[N-({[7-(methanesulfonyl)-7-azaspiro[3.5]nonan-2-yl]oxy}carbonyl)-L-leucyl]amino}-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid, (1S,2S)-1-hydroxy-2-{[N-({[7-(methanesulfonyl)-7-azaspiro[3.5]nonan-2-yl]oxy}carbonyl)-L-leucyl]amino}-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid, ... (4 entities in total)
Functional Keywordscovid-19, protease, severe acute respiratory syndrome coronavirus 2, sars-cov-2 3cl protease inhhibitors, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
Biological sourceSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, 2019-nCoV)
Total number of polymer chains2
Total formula weight70524.47
Authors
Lovell, S.,Liu, L.,Battaile, K.P.,Chamandi, S.D.,Kim, Y.,Groutas, W.C.,Chang, K.O. (deposition date: 2021-12-09, release date: 2021-12-22, Last modification date: 2023-10-18)
Primary citationDampalla, C.S.,Rathnayake, A.D.,Galasiti Kankanamalage, A.C.,Kim, Y.,Perera, K.D.,Nguyen, H.N.,Miller, M.J.,Madden, T.K.,Picard, H.R.,Thurman, H.A.,Kashipathy, M.M.,Liu, L.,Battaile, K.P.,Lovell, S.,Chang, K.O.,Groutas, W.C.
Structure-Guided Design of Potent Spirocyclic Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 3C-like Protease.
J.Med.Chem., 65:7818-7832, 2022
Cited by
PubMed Abstract: The worldwide impact of the ongoing COVID-19 pandemic on public health has made imperative the discovery and development of direct-acting antivirals aimed at targeting viral and/or host targets. SARS-CoV-2 3C-like protease (3CL) has emerged as a validated target for the discovery of SARS-CoV-2 therapeutics because of the pivotal role it plays in viral replication. We describe herein the structure-guided design of highly potent inhibitors of SARS-CoV-2 3CL that incorporate in their structure novel spirocyclic design elements aimed at optimizing potency by accessing new chemical space. Inhibitors of both SARS-CoV-2 3CL and MERS-CoV 3CL that exhibit nM potency and high safety indices have been identified. The mechanism of action of the inhibitors and the structural determinants associated with binding were established using high-resolution cocrystal structures.
PubMed: 35638577
DOI: 10.1021/acs.jmedchem.2c00224
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.75 Å)
Structure validation

227111

數據於2024-11-06公開中

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