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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. The provisional RefSeq YP_009725301 has been allocated to SARS-CoV-2 M |
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| 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 | |
| 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 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| PRD_002214 (N3) inhibits SARS-CoV-2 plaque formation in Vero cell culture with an IC50 of 16.77 μM [23]. The MERS-CoV inhibitor compound 11r [PMID: 32045235] is active against SARS-CoV-2 [51]. Baker et al. (2021) performed a large scale repurposing screen, which corroborated the inhibitory activity of boceprevir (and other hepatitis C NS3/4A protease inhibitors) against SARS-CoV-2 Mpro [4]. Chia et al. published a review of patents claiming coronavirus 3CLpro inhibitors in October 2021 [9]. |
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| Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| General Comments |
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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 [35]. 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) [43]. 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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