Target Information
| Target General Infomation | Top | ||||
|---|---|---|---|---|---|
| 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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| Target Status |
Target in Preclinical Study
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[1] | |||
| Disease | [+] 1 Target-related Diseases | + | |||
| 1 | Middle East Respiratory Syndrome [ICD-11: 1D64] | ||||
| 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 |
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| Drugs and Modes of Action | Top | ||||
|---|---|---|---|---|---|
| Preclinical Drugs | [+] 3 Preclinical Drugs | + | |||
| 1 | Thioguanine | Drug Info | Preclinical | MERS | [1] |
| 2 | Mercaptopurine | Drug Info | Preclinical | MERS | [1] |
| 3 | PMID30940566-compound-6 | Drug Info | Preclinical | MERS | [2] |
| Investigative agents | [+] 2 Investigative agents | + | |||
| 1 | Disulfiram | Drug Info | Investigative | MERS | [3] |
| 2 | Mycophenolic acid | Drug Info | Investigative | MERS | [4] |
| Mode of Action | [+] 1 Modes of Action | + | |||
| Inhibitor | [+] 5 Inhibitor drugs | + | |||
| 1 | Disulfiram | Drug Info | [3] | ||
| 2 | Mercaptopurine | Drug Info | [1] | ||
| 3 | PMID30940566-compound-6 | Drug Info | [2] | ||
| 4 | Thioguanine | Drug Info | [1] | ||
| 5 | Mycophenolic acid | Drug Info | [4] | ||
| References | Top | ||||
|---|---|---|---|---|---|
| 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. | ||||
| 2 | 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. | ||||
| 3 | Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150. | ||||
| 4 | SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug;14(8):523-34. | ||||
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