Target Information
Target General Information | Top | |||||
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Target ID |
T18143
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Target Name |
MERS-CoV papain-like proteinase (PL-PRO)
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Synonyms |
MERS-CoV PLpro; MERS-CoV Non-structural protein 3; MERS-CoV nsp3
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Gene Name |
MERS-CoV rep; MERS-CoV 1a-1b
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Disease | [+] 3 Target-related Diseases | + | ||||
1 | Crohn disease [ICD-11: DD70] | |||||
2 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
3 | 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 |
APVKKVAFGGDQVHEVAAVRSVTVEYNIHAVLDTLLASSSLRTFVVDKSLSIEEFADVVK
EQVSDLLVKLLRGMPIPDFDLDDFIDAPCYCFNAEGDASWSSTMIFSLHPVECDEECSEV EASDLEEGESECISETSTEQVDVSHEISDDEWAAAVDEAFPLDEAEDVTESVQEEAQPVE VPVEDIAQVVIADTLQETPVVSDTVEVPPQVVKLPSEPQTIQPEVKEVAPVYEADTEQTQ SVTVKPKRLRKKRNVDPLSNFEHKVITECVTIVLGDAIQVAKCYGESVLVNAANTHLKHG GGIAGAINAASKGAVQKESDEYILAKGPLQVGDSVLLQGHSLAKNILHVVGPDARAKQDV SLLSKCYKAMNAYPLVVTPLVSAGIFGVKPAVSFDYLIREAKTRVLVVVNSQDVYKSLTI VDIPQSLTFSYDGLRGAIRKAKDYGFTVFVCTDNSANTKVLRNKGVDYTKKFLTVDGVQY YCYTSKDTLDDILQQANKSVGIISMPLGYVSHGLDLIQAGSVVRRVNVPYVCLLANKEQE AILMSEDVKLNPSEDFIKHVRTNGGYNSWHLVEGELLVQDLRLNKLLHWSDQTICYKDSV FYVVKNSTAFPFETLSACRAYLDSRTTQQLTIEVLVTVDGVNFRTVVLNNKNTYRSQLGC VFFNGADISDTIPDEKQNGHSLYLADNLTADETKALKELYGPVDPTFLHRFYSLKAAVHK WKMVVCDKVRSLKLSDNNCYLNAVIMTLDLLKDIKFVIPALQHAFMKHKGGDSTDFIALI MAYGNCTFGAPDDASRLLHTVLAKAELCCSARMVWREWCNVCGIKDVVLQGLKACCYVGV QTVEDLRARMTYVCQCGGERHRQIVEHTTPWLLLSGTPNEKLVTTSTAPDFVAFNVFQGI ETAVGHYVHARLKGGLILKFDSGTVSKTSDWKCKVTDVLFPGQKYSSDCNVVRYSLDGNF RTEVDPDLSAFYVKDGKYFTSEPPVTYSPATILAGSVYTNSCLVSSDGQPGGDAISLSFN NLLGFDSSKPVTKKYTYSFLPKEDGDVLLAEFDTYDPIYKNGAMYKGKPILWVNKASYDT NLNKFNRASLRQIFDVAPIELENKFTPLSVESTPVEPPTVDVVALQQEMTIVKCKGLNKP FVKDNVSFVADDSGTPVVEYLSKEDLHTLYVDPKYQVIVLKDNVLSSMLRLHTVESGDIN VVAASGSLTRKVKLLFRASFYFKEFATRTFTATTAVGSCIKSVVRHLGVTKGILTGCFSF VKMLFMLPLAYFSDSKLGTTEVKVSALKTAGVVTGNVVKQCCTAAVDLSMDKLRRVDWKS TLRLLLMLCTTMVLLSSVYHLYVFNQVLSSDVMFEDAQGLKKFYKEVRAYLGISSACDGL ASAYRANSFDVPTFCANRSAMCNWCLISQDSITHYPALKMVQTHLSHYVLNIDWLWFAFE TGLAYMLYTSAFNWLLLAGTLHYFFAQTSIFVDWRSYNYAVSSAFWLFTHIPMAGLVRMY NLLACLWLLRKFYQHVINGCKDTACLLCYKRNRLTRVEASTVVCGGKRTFYITANGGISF CRRHNWNCVDCDTAGVGNTFICEEVANDLTTALRRPINATDRSHYYVDSVTVKETVVQFN YRRDGQPFYERFPLCAFTNLDKLKFKEVCKTTTGIPEYNFIIYDSSDRGQESLARSACVY YSQVLCKSILLVDSSLVTSVGDSSEIATKMFDSFVNSFVSLYNVTRDKLEKLISTARDGV RRGDNFHSVLTTFIDAARGPAGVESDVETNEIVDSVQYAHKHDIQITNESYNNYVPSYVK PDSVSTSDLGSLIDCNAASVNQIVLRNSNGACIWNAAAYMKLSDALKRQIRIACRKCNLA FRLTTSKLRANDNILSVRFTANKIVGG Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Drugs in Phase 2 Trial | [+] 1 | + | ||||
1 | Disulfiram | Drug Info | Approved | Alcohol dependence | [2] | |
Preclinical Drugs | [+] 3 | + | ||||
1 | Mercaptopurine | Drug Info | Approved | Acute lymphocytic leukaemia | [2] | |
2 | Thioguanine | Drug Info | Approved | Acute lymphocytic leukaemia | [2] | |
3 | PMID30940566-compound-6 | Drug Info | Preclinical | Middle East Respiratory Syndrome (MERS) | [3] | |
Investigative Agents | [+] 1 | + | ||||
1 | Mycophenolic acid | Drug Info | Approved | Crohn disease | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 5 Inhibitor drugs | + | ||||
1 | Disulfiram | Drug Info | [4] | |||
2 | Mercaptopurine | Drug Info | [1] | |||
3 | PMID30940566-compound-6 | Drug Info | [3] | |||
4 | Thioguanine | Drug Info | [1] | |||
5 | Mycophenolic acid | Drug Info | [5] |
Chemical Structure based Activity Landscape of Target | Top |
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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 | Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus. Antiviral Res. 2015 Mar;115:9-16. | |||||
REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 3 | Identification and Design of Novel Small Molecule Inhibitors Against MERS-CoV Papain-Like Protease via High-Throughput Screening and Molecular Modeling Bioorg Med Chem. 2019 May 15;27(10):1981-1989. | |||||
REF 4 | Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150. | |||||
REF 5 | SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34. |
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