Target General Infomation
Target ID
T87325
Target Name
COVID-19 papain-like proteinase (PL-PRO)
Synonyms
COVID-19 papain-like proteinase; COVID-19 PL2-PRO; COVID-19 PL-PRO; COVID-19 main proteinase; COVID-19 non-structural protein 3
Gene Name
COVID-19 rep; COVID-19 1a-1b
Target Status
Target in Phase 3 Trial
[1]
Disease [+] 1 Target-related Diseases +
1 COVID-19 [ICD-11: 1D6Y]
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.
BioChemical Class
Coronaviruses polyprotein 1ab family
UniProt ID
R1AB_SARS2(819-2763)
EC Number
EC 3.4.19.12
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
Drugs and Modes of Action
Drugs in Phase 3 Trial [+] 1 Drugs in Phase 3 Trial +
1 Isotretinoin Drug Info Phase 3 Trial COVID-19 [2]
Investigative agents [+] 9 Investigative agents +
1 PMID26868298-compound-N3 Drug Info Investigative COVID-19 [1]
2 PX-12 Drug Info Investigative COVID-19 [1]
3 Hexylcarbamoyl fluorouracil Drug Info Investigative COVID-19 [1]
4 SPI-1005 Drug Info Investigative COVID-19 [1]
5 Disulfiram Drug Info Investigative COVID-19 [1]
6 Isoarnebin 4 Drug Info Investigative COVID-19 [1]
7 Tideglusib Drug Info Investigative COVID-19 [1]
8 PMID32321856-compound-11a Drug Info Investigative COVID-19 [3]
9 PMID32321856-compound-11b Drug Info Investigative COVID-19 [3]
Mode of Action [+] 1 Modes of Action +
Inhibitor [+] 10 Inhibitor drugs +
1 Isotretinoin Drug Info [2]
2 Disulfiram Drug Info [1]
3 SPI-1005 Drug Info [1]
4 PMID26868298-compound-N3 Drug Info [1]
5 Hexylcarbamoyl fluorouracil Drug Info [1]
6 Isoarnebin 4 Drug Info [1]
7 PMID32321856-compound-11a Drug Info [3]
8 PMID32321856-compound-11b Drug Info [3]
9 PX-12 Drug Info [1]
10 Tideglusib Drug Info [1]
References
1 Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9.
2 ClinicalTrials.gov (NCT04361422) Isotretinoin in Treatment of COVID-19. U.S. National Institutes of Health.
3 Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease. Science. 2020 Apr 22;eabb4489.

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