Target Information
| Target General Information | Top | |||||
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| Target ID |
T87325
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| Target Name |
COVID-19 papain-like proteinase (PL-PRO)
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| Synonyms |
COVID-19 papain-like proteinase; COVID-19 PL2-PRO; COVID-19 PL-PRO; COVID-19 main proteinase; COVID-19 non-structural protein 3
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| Gene Name |
COVID-19 rep; COVID-19 1a-1b
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Substance abuse [ICD-11: 6C40] | |||||
| Function |
Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.
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| BioChemical Class |
Coronaviruses polyprotein 1ab family
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| UniProt ID | ||||||
| EC Number |
EC 3.4.19.12
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| Sequence |
APTKVTFGDDTVIEVQGYKSVNITFELDERIDKVLNEKCSAYTVELGTEVNEFACVVADA
VIKTLQPVSELLTPLGIDLDEWSMATYYLFDESGEFKLASHMYCSFYPPDEDEEEGDCEE EEFEPSTQYEYGTEDDYQGKPLEFGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQ TTTIQTIVEVQPQLEMELTPVVQTIEVNSFSGYLKLTDNVYIKNADIVEEAKKVKPTVVV NAANVYLKHGGGVAGALNKATNNAMQVESDDYIATNGPLKVGGSCVLSGHNLAKHCLHVV GPNVNKGEDIQLLKSAYENFNQHEVLLAPLLSAGIFGADPIHSLRVCVDTVRTNVYLAVF DKNLYDKLVSSFLEMKSEKQVEQKIAEIPKEEVKPFITESKPSVEQRKQDDKKIKACVEE VTTTLEETKFLTENLLLYIDINGNLHPDSATLVSDIDITFLKKDAPYIVGDVVQEGVLTA VVIPTKKAGGTTEMLAKALRKVPTDNYITTYPGQGLNGYTVEEAKTVLKKCKSAFYILPS IISNEKQEILGTVSWNLREMLAHAEETRKLMPVCVETKAIVSTIQRKYKGIKIQEGVVDY GARFYFYTSKTTVASLINTLNDLNETLVTMPLGYVTHGLNLEEAARYMRSLKVPATVSVS SPDAVTAYNGYLTSSSKTPEEHFIETISLAGSYKDWSYSGQSTQLGIEFLKRGDKSVYYT SNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDNINLHTQVVDMSMTYGQQFGPTY LDGADVTKIKPHNSHEGKTFYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALNHTKKWKY PQVNGLTSIKWADNNCYLATALLTLQQIELKFNPPALQDAYYRARAGEAANFCALILAYC NKTVGELGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQ FKKGVQIPCTCGKQATKYLVQQESPFVMMSAPPAQYELKHGTFTCASEYTGNYQCGHYKH ITSKETLYCIDGALLTKSSEYKGPITDVFYKENSYTTTIKPVTYKLDGVVCTEIDPKLDN YYKKDNSYFTEQPIDLVPNQPYPNASFDNFKFVCDNIKFADDLNQLTGYKKPASRELKVT FFPDLNGDVVAIDYKHYTPSFKKGAKLLHKPIVWHVNNATNKATYKPNTWCIRCLWSTKP VETSNSFDVLKSEDAQGMDNLACEDLKPVSEEVVENPTIQKDVLECNVKTTEVVGDIILK PANNSLKITEEVGHTDLMAAYVDNSSLTIKKPNELSRVLGLKTLATHGLAAVNSVPWDTI ANYAKPFLNKVVSTTTNIVTRCLNRVCTNYMPYFFTLLLQLCTFTRSTNSRIKASMPTTI AKNTVKSVGKFCLEASFNYLKSPNFSKLINIIIWFLLLSVCLGSLIYSTAALGVLMSNLG MPSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSGLDSLDTYPSLETIQITISSFKWDL TAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVHFISNSWLMWLIINLVQMAPIS AMVRMYIFFASFYYVWKSYVHVVDGCNSSTCMMCYKRNRATRVECTTIVNGVRRSFYVYA NGGKGFCKLHNWNCVNCDTFCAGSTFISDEVARDLSLQFKRPINPTDQSSYIVDSVTVKN GSIHLYFDKAGQKTYERHSLSHFVNLDNLRANNTKGSLPINVIVFDGKSKCEESSAKSAS VYYSQLMCQPILLLDQALVSDVGDSAEVAVKMFDAYVNTFSSTFNVPMEKLKTLVATAEA ELAKNVSLDNVLSTFISAARQGFVDSDVETKDVVECLKLSHQSDIEVTGDSCNNYMLTYN KVENMTPRDLGACIDCSARHINAQVAKSHNIALIWNVKDFMSLSEQLRKQIRSAAKKNNL PF Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Drugs in Phase 2 Trial | [+] 2 | + | ||||
| 1 | Disulfiram | Drug Info | Approved | Alcohol dependence | [2] | |
| 2 | SPI-1005 | Drug Info | Phase 2b | Meniere disease | [4] | |
| Drugs in Phase 3 Trial | [+] 1 | + | ||||
| 1 | Isotretinoin | Drug Info | Phase 3 | Coronavirus Disease 2019 (COVID-19) | [3] | |
| Investigative Agents | [+] 2 | + | ||||
| 1 | PX-12 | Drug Info | Phase 2 | Pancreatic cancer | [5] | |
| 2 | Tideglusib | Drug Info | Phase 2 | Alzheimer disease | [6] | |
| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | GRL0617 | Drug Info | Preclinical | Coronavirus infection | [7] | |
| Preclinical Drugs | [+] 1 | + | ||||
| 1 | PMID26868298-compound-N3 | Drug Info | Preclinical | Severe acute respiratory syndrome (SARS) | [7] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 11 Inhibitor drugs | + | ||||
| 1 | Isotretinoin | Drug Info | [3] | |||
| 2 | Disulfiram | Drug Info | [1] | |||
| 3 | SPI-1005 | Drug Info | [1] | |||
| 4 | GRL0617 | Drug Info | [8] | |||
| 5 | PMID26868298-compound-N3 | Drug Info | [1] | |||
| 6 | Hexylcarbamoyl fluorouracil | Drug Info | [1] | |||
| 7 | Isoarnebin 4 | Drug Info | [1] | |||
| 8 | PMID32321856-compound-11a | Drug Info | [9] | |||
| 9 | PMID32321856-compound-11b | Drug Info | [9] | |||
| 10 | PX-12 | Drug Info | [1] | |||
| 11 | Tideglusib | Drug Info | [1] | |||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| References | Top | |||||
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| REF 1 | Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | ClinicalTrials.gov (NCT04361422) Isotretinoin in Treatment of COVID-19. U.S. National Institutes of Health. | |||||
| REF 4 | Sound Pharmaceuticals announces positive topline results from the SPI-1005 Phase 2b Meniere's Disease clinical trial. Jun 25, 2019 | |||||
| REF 5 | A Randomized Phase II Study of PX-12, an Inhibitor of Thioredoxin in Patients With Advanced Cancer of the Pancreas Following Progression After a Gemcitabine-Containing Combination. Cancer Chemother Pharmacol. 2011 Mar;67(3):503-9. | |||||
| REF 6 | A Phase II Trial of Tideglusib in Alzheimer's Disease. J Alzheimers Dis. 2015;45(1):75-88. | |||||
| REF 7 | Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47. | |||||
| REF 8 | Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2021 Jan;11(1):237-245. | |||||
| REF 9 | Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science. 2020 Apr 22;eabb4489. | |||||
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