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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| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Proflavine | Ligand Info | |||||
| Structure Description | X-ray structure of SCoV2-PLpro in complex with small molecule inhibitor | PDB:7NT4 | ||||
| Method | X-ray diffraction | Resolution | 2.68 Å | Mutation | No | [8] |
| PDB Sequence |
FTTVDNINLH
18 TQVVDMSMTY28 GQQFGPTYLD38 GADVTKIKPH48 NSHEGKTFYV58 LPNDDTLRVE 68 AFEYYHTTDP78 SFLGRYMSAL88 NHTKKWKYPQ98 VNGLTSIKWA108 DNNCYLATAL 118 LTLQQIELKF128 NPPALQDAYY138 RARAGEAANF148 CALILAYCNK158 TVGELGDVRE 168 TMSYLFQHAN178 LDSCKRVLNV188 VCKTCGQQQT198 TLKGVEAVMY208 MGTLSYEQFK 218 KGVQIPCTCG228 KQATKYLVQQ238 ESPFVMMSAP248 PAQYELKHGT258 FTCASEYTGN 268 YQCGHYKHIT278 SKETLYCIDG288 ALLTKSSEYK298 GPITDVFYKE308 NSYTTTIK |
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TRP107
3.745
LEU163
4.608
GLY164
2.767
ASP165
2.766
ARG167
4.146
MET209
3.621
ALA247
4.642
PRO248
3.593
PRO249
3.417
TYR265
3.264
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| Ligand Name: Caffeine | Ligand Info | |||||
| Structure Description | The crystal structure of SARS-CoV-2 papain-like protease in apo form | PDB:7D7K | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | Yes | [9] |
| PDB Sequence |
TIKVFTTVDN
13 INLHTQVVDM23 SMTYGQQFGP33 TYLDGADVTK43 IKPHNSHEGK53 TFYVLPNDDT 63 LRVEAFEYYH73 TTDPSFLGRY83 MSALNHTKKW93 KYPQVNGLTS103 IKWADNNSYL 113 ATALLTLQQI123 ELKFNPPALQ133 DAYYRARAGE143 AANFCALILA153 YCNKTVGELG 163 DVRETMSYLF173 QHANLDSCKR183 VLNVVCKTCG193 QQQTTLKGVE203 AVMYMGTLSY 213 EQFKKGVQIP223 CTCGKQATKY233 LVQQESPFVM243 MSAPPAQYEL253 KHGTFTCASE 263 YTGNYQCGHY273 KHITSKETLY283 CIDGALLTKS293 SEYKGPITDV303 FYKENSYTTT 313 IK
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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 | |||||
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| 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 | Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses. Cell Chem Biol. 2022 May 19;29(5):774-784.e8. | |||||
| REF 9 | High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors. Protein Cell. 2021 Nov;12(11):877-888. | |||||
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