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Gene and Protein Information ![]() |
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Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
SARS-CoV-2 | - | 306 | ||||
SARS-CoV | - | 306 | ||||
Gene and Protein Information Comments | ||||||
The SARS-CoV main protease (Mpro) is a 306 amino acid cysteine protease that is encoded in the viral RNA replicase gene. It is amino acids 3241-3546 of the full length SARS-CoV polyprotein (3919 amino acids). The SARS-CoV-2 Mpro is also 306 amino acids (3264-3569 of the full length polyprotein). The RefSeq YP_009725301 was allocated to SARS-CoV-2 Mpro. The protein has been crystalised in complex with the inhibitor PRD_002214 (N3), and the structure was submitted to the RCSB Protein Databank with ID 6LU7 [44]. The UniProt ID P0DTD1 refers to the complete SARS-CoV-2 replicase polyprotein (length 7096 amino acids). Mpro has been assigned the IUBMB enzyme nomenclature identifier EC 3.4.22.69. |
Previous and Unofficial Names ![]() |
3c-like proteinase | SARS-CoV-2 Mpro | Chain A, 3c-like Proteinase | 3CL protease | Mpro | nsp5 |
Database Links ![]() |
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ChEMBL Target | CHEMBL3927 (SARS-CoV) |
RefSeq Protein | YP_009725301 (SARS-CoV-2) |
UniProtKB | P0C6U8 (SARS-CoV) |
Selected 3D Structures ![]() |
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EC number (SARS-CoV-2) |
3.4.22.69 |
Download all structure-activity data for this target as a CSV file
Other Binding Ligands | |||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||
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General Comments |
The coronavirus (CoV) main proteases (Mpro) are cysteine proteases that are encoded in the viral RNA replicase gene. Mpro catalyses the proteolytic processing (cleavage) of replicase precursor polyproteins in to discrete functional proteins. In total There are 11 Mpro cleavage site within the C-terminus of the replicase polyprotein. Mpro plays a central role in the viral life cycle, and in light of evidence from other coronaviruses, SARS-CoV Mpro was a lead target for antiviral drug discovery. Many of the compounds that were discovered to inhibit the activity of MERS- and SARS-CoV Mpro enzymes have been tested for activity against SARS-CoV-2 [68]. Inhibitor design and development in response to SARS-CoV-2 has been intense [47]. Mpro has been reported to induce damage to the microvascular network in the brain, via proteolytic cleavage and inactivation of the endothelially-expressed protein NEMO (an essential NF-κB modulator with a central role in immunity; HGNC symbol IKBKG) [85]. Depletion of NEMO leads to cell death, and this cell death is dependent on receptor-interacting protein kinase 3 (RIPK3) signalling. A small molecule inhibitor of RIPK1, an upstream kinase that activates RIPK3, was shown to block the Mpro-induced microvascular pathology. It is interesting to note that a RIPK1 inhibitor (SAR443122) is already under clinical evaluation in COVID-19 patients. Although Mpro is strictly a component of the CoV replicase polyprotein(s) 1a and 1ab, we have included it as a separate entity to allow us to more sensibly curate pharmacological information (particularly regarding inhibitor development) that is specific for this protease, and to facilitate data retrieval. |
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