Target Information
| Target General Information | Top | |||||
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| Target ID |
T88015
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| Target Name |
COVID-19 3C-like protease (3CLpro)
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| Synonyms |
COVID-19 3CL-PRO; COVID-19 3CLp; COVID-19 nsp5
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| Gene Name |
COVID-19 rep
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Human immunodeficiency virus disease [ICD-11: 1C60-1C62] | |||||
| Function |
Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Also able to bind an ADP-ribose-1''-phosphate (ADRP).
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| BioChemical Class |
Coronaviruses polyprotein 1ab family
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| UniProt ID | ||||||
| EC Number |
EC 3.4.22.69
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| Sequence |
SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIR
KSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNG SPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGN FYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYE PLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQC SGVTFQ Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Drugs in Phase 3 Trial | [+] 6 | + | ||||
| 1 | Lopinavir + ritonavir | Drug Info | Approved | Human immunodeficiency virus infection | [2] | |
| 2 | ASC09 + ritonavir + oseltamivir | Drug Info | Phase 3 | Coronavirus Disease 2019 (COVID-19) | [3] | |
| 3 | Darunavir + cobicistat | Drug Info | Phase 3 | Coronavirus Disease 2019 (COVID-19) | [4] | |
| 4 | Lopinavir + ritonavir + favipiravir | Drug Info | Phase 3 | Coronavirus Disease 2019 (COVID-19) | [5] | |
| 5 | Lopinavir + ritonavir + oseltamivir | Drug Info | Phase 3 | Coronavirus Disease 2019 (COVID-19) | [5] | |
| 6 | ASC09 + ritonavir | Drug Info | Phase 1 | Coronavirus Disease 2019 (COVID-19) | [7] | |
| Drugs in Phase 2 Trial | [+] 1 | + | ||||
| 1 | Lopinavir + ritonavir + ribavirin + interferon beta-1b | Drug Info | Phase 2 | Coronavirus Disease 2019 (COVID-19) | [6] | |
| Drugs in Phase 1 Trial | [+] 1 | + | ||||
| 1 | Lopinavir + ritonavir + interferon apha + traditional chinese medicines granules | Drug Info | Phase 1 | Coronavirus Disease 2019 (COVID-19) | [8] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | PF-07817883 | Drug Info | Phase 1 | Coronavirus Disease 2019 (COVID-19) | [9] | |
| Preclinical Drugs | [+] 2 | + | ||||
| 1 | GC376 | Drug Info | Preclinical | Severe acute respiratory syndrome (SARS) | [10] | |
| 2 | Lopinavir + ritonavir + interferon alpha | Drug Info | Preclinical | Coronavirus Disease 2019 (COVID-19) | [12] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | GRL001 | Drug Info | Preclinical | Coronavirus infection | [11] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 13 Inhibitor drugs | + | ||||
| 1 | ASC09 + ritonavir | Drug Info | [1] | |||
| 2 | ASC09 + ritonavir + oseltamivir | Drug Info | [1] | |||
| 3 | Darunavir + cobicistat | Drug Info | [1] | |||
| 4 | Lopinavir + ritonavir | Drug Info | [1] | |||
| 5 | Lopinavir + ritonavir + favipiravir | Drug Info | [1] | |||
| 6 | Lopinavir + ritonavir + oseltamivir | Drug Info | [1] | |||
| 7 | Lopinavir + ritonavir + ribavirin + interferon beta-1b | Drug Info | [1] | |||
| 8 | Lopinavir + ritonavir + interferon apha + traditional chinese medicines granules | Drug Info | [1] | |||
| 9 | PF-07817883 | Drug Info | [9] | |||
| 10 | GC376 | Drug Info | [13] | |||
| 11 | GRL001 | Drug Info | [11] | |||
| 12 | Lopinavir + ritonavir + interferon alpha | Drug Info | [1] | |||
| 13 | Boceprevir | Drug Info | [13] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Vitamin C | Ligand Info | |||||
| Structure Description | SARS Coronavirus-2 Main Protease 3CL-pro binding Ascorbate | PDB:7MPB | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [14] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGV |
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| Ligand Name: Sulfapyridine | Ligand Info | |||||
| Structure Description | PanDDA analysis group deposition -- Crystal Structure of SARS-CoV-2 main protease in complex with Z271004858 | PDB:5RF8 | ||||
| Method | X-ray diffraction | Resolution | 1.44 Å | Mutation | No | [15] |
| PDB Sequence |
SGFRKMAFPS
10 GKVEGCMVQV20 TCGTTTLNGL30 WLDDVVYCPR40 HVICTSEDML50 NPNYEDLLIR 60 KSNHNFLVQA70 GNVQLRVIGH80 SMQNCVLKLK90 VDTANPKTPK100 YKFVRIQPGQ 110 TFSVLACYNG120 SPSGVYQCAM130 RPNFTIKGSF140 LNGSCGSVGF150 NIDYDCVSFC 160 YMHHMELPTG170 VHAGTDLEGN180 FYGPFVDRQT190 AQAAGTDTTI200 TVNVLAWLYA 210 AVINGDRWFL220 NRFTTTLNDF230 NLVAMKYNYE240 PLTQDHVDIL250 GPLSAQTGIA 260 VLDMCASLKE270 LLQNGMNGRT280 ILGSALLEDE290 FTPFDVVRQC300 SGVT |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| References | Top | |||||
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| REF 1 | Coronavirus puts drug repurposing on the fast track. Nat Biotechnol. 2020 Apr;38(4):379-381. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | ClinicalTrials.gov (NCT04261270) A Randomized,Open,Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia | |||||
| REF 4 | ClinicalTrials.gov (NCT04252274) Efficacy and Safety of Darunavir and Cobicistat for Treatment of COVID-19 | |||||
| REF 5 | ClinicalTrials.gov (NCT04303299) Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID-19 : A Randomized Control Trial | |||||
| REF 6 | ClinicalTrials.gov (NCT04276688) Lopinavir/ Ritonavir, Ribavirin and IFN-beta Combination for nCoV Treatment | |||||
| REF 7 | ClinicalTrials.gov (NCT04261907) Evaluating and Comparing the Safety and Efficiency of ASC09/Ritonavir and Lopinavir/Ritonavir for Novel Coronavirus Infection | |||||
| REF 8 | ClinicalTrials.gov (NCT04251871) Treatment and Prevention of Traditional Chinese Medicines (TCMs) on 2019-nCoV Infection | |||||
| REF 9 | ClinicalTrials.gov (NCT05580003) COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE RELATIVE BIOAVAILABILITY AND FOOD EFFECT OF SOLID ORAL FORMULATION AND OPTIONAL OPEN-LABEL, NON-RANDOMIZED STUDY TO EVALUATE METABOLISM AND EXCRETION OF PF-07817883 AND OPTIONAL RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE EFFECT OF PF-07817883 ON PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY ADULT PARTICIPANTS. U.S.National Institutes of Health. | |||||
| REF 10 | Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor. PLoS Pathog. 2016 Mar 30;12(3):e1005531. | |||||
| REF 11 | Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47. | |||||
| REF 12 | ClinicalTrials.gov (NCT04275388) Xiyanping Injection for the Treatment of New Coronavirus Infected Pneumonia | |||||
| REF 13 | Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. 2020. April 20. doi: https://doi.org/10.1101/2020.04.20.051581 | |||||
| REF 14 | Vitamin C inhibits SARS coronavirus-2 main protease essential for viral replication. doi:10.1101/2021.05.02.442358. | |||||
| REF 15 | Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease. Nat Commun. 2020 Oct 7;11(1):5047. | |||||
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