Target Information
| Target General Infomation | Top | ||||
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| Target ID |
T89736
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| Target Name |
SARS-CoV papain-like proteinase (PL-PRO)
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| Synonyms |
SARS-CoV papain-like proteinase; SARS-CoV PL2-PRO; SARS-CoV PL-PRO; SARS-CoV SARS coronavirus main proteinase; Non-structural protein 3
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| Gene Name |
SARS-CoV rep; SARS-CoV 1a-1b
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| Target Status |
Target in Preclinical Study
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[1] | |||
| Disease | [+] 1 Target-related Diseases | + | |||
| 1 | Severe acute respiratory syndrome [ICD-11: 1D65] | ||||
| 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. Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication. Nsp3, nsp4 and nsp6 together are sufficient to form DMV. 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 |
PIKGVTFGEDTVWEVQGYKNVRITFELDERVDKVLNEKCSVYTVESGTEVTEFACVVAEA
VVKTLQPVSDLLTNMGIDLDEWSVATFYLFDDAGEENFSSRMYCSFYPPDEEEEDDAECE EEEIDETCEHEYGTEDDYQGLPLEFGASAETVRVEEEEEEDWLDDTTEQSEIEPEPEPTP EEPVNQFTGYLKLTDNVAIKCVDIVKEAQSANPMVIVNAANIHLKHGGGVAGALNKATNG AMQKESDDYIKLNGPLTVGGSCLLSGHNLAKKCLHVVGPNLNAGEDIQLLKAAYENFNSQ DILLAPLLSAGIFGAKPLQSLQVCVQTVRTQVYIAVNDKALYEQVVMDYLDNLKPRVEAP KQEEPPNTEDSKTEEKSVVQKPVDVKPKIKACIDEVTTTLEETKFLTNKLLLFADINGKL YHDSQNMLRGEDMSFLEKDAPYMVGDVITSGDITCVVIPSKKAGGTTEMLSRALKKVPVD EYITTYPGQGCAGYTLEEAKTALKKCKSAFYVLPSEAPNAKEEILGTVSWNLREMLAHAE ETRKLMPICMDVRAIMATIQRKYKGIKIQEGIVDYGVRFFFYTSKEPVASIITKLNSLNE PLVTMPIGYVTHGFNLEEAARCMRSLKAPAVVSVSSPDAVTTYNGYLTSSSKTSEEHFVE TVSLAGSYRDWSYSGQRTELGVEFLKRGDKIVYHTLESPVEFHLDGEVLSLDKLKSLLSL REVKTIKVFTTVDNTNLHTQLVDMSMTYGQQFGPTYLDGADVTKIKPHVNHEGKTFFVLP SDDTLRSEAFEYYHTLDESFLGRYMSALNHTKKWKFPQVGGLTSIKWADNNCYLSSVLLA LQQLEVKFNAPALQEAYYRARAGDAANFCALILAYSNKTVGELGDVRETMTHLLQHANLE SAKRVLNVVCKHCGQKTTTLTGVEAVMYMGTLSYDNLKTGVSIPCVCGRDATQYLVQQES SFVMMSAPPAEYKLQQGTFLCANEYTGNYQCGHYTHITAKETLYRIDGAHLTKMSEYKGP VTDVFYKETSYTTTIKPVSYKLDGVTYTEIEPKLDGYYKKDNAYYTEQPIDLVPTQPLPN ASFDNFKLTCSNTKFADDLNQMTGFTKPASRELSVTFFPDLNGDVVAIDYRHYSASFKKG AKLLHKPIVWHINQATTKTTFKPNTWCLRCLWSTKPVDTSNSFEVLAVEDTQGMDNLACE SQQPTSEEVVENPTIQKEVIECDVKTTEVVGNVILKPSDEGVKVTQELGHEDLMAAYVEN TSITIKKPNELSLALGLKTIATHGIAAINSVPWSKILAYVKPFLGQAAITTSNCAKRLAQ RVFNNYMPYVFTLLFQLCTFTKSTNSRIRASLPTTIAKNSVKSVAKLCLDAGINYVKSPK FSKLFTIAMWLLLLSICLGSLICVTAAFGVLLSNFGAPSYCNGVRELYLNSSNVTTMDFC EGSFPCSICLSGLDSLDSYPALETIQVTISSYKLDLTILGLAAEWVLAYMLFTKFFYLLG LSAIMQVFFGYFASHFISNSWLMWFIISIVQMAPVSAMVRMYIFFASFYYIWKSYVHIMD GCTSSTCMMCYKRNRATRVECTTIVNGMKRSFYVYANGGRGFCKTHNWNCLNCDTFCTGS TFISDEVARDLSLQFKRPINPTDQSSYIVDSVAVKNGALHLYFDKAGQKTYERHPLSHFV NLDNLRANNTKGSLPINVIVFDGKSKCDESASKSASVYYSQLMCQPILLLDQALVSDVGD STEVSVKMFDAYVDTFSATFSVPMEKLKALVATAHSELAKGVALDGVLSTFVSAARQGVV DTDVDTKDVIECLKLSHHSDLEVTGDSCNNFMLTYNKVENMTPRDLGACIDCNARHINAQ VAKSHNVSLIWNVKDYMSLSEQLRKQIRSAAKKNNIPFRLTCATTRQVVNVITTKISLKG G |
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| Drugs and Modes of Action | Top | ||||
|---|---|---|---|---|---|
| Preclinical Drugs | [+] 2 Preclinical Drugs | + | |||
| 1 | Thioguanine | Drug Info | Preclinical | SARS | [1] |
| 2 | Mercaptopurine | Drug Info | Preclinical | SARS | [1] |
| Investigative agents | [+] 3 Investigative agents | + | |||
| 1 | Disulfiram | Drug Info | Investigative | SARS | [2] |
| 2 | GRL-0667 | Drug Info | Investigative | SARS | [3] |
| 3 | PMID20527968-compound-6577871 | Drug Info | Investigative | SARS | [3] |
| Mode of Action | [+] 1 Modes of Action | + | |||
| Inhibitor | [+] 5 Inhibitor drugs | + | |||
| 1 | Disulfiram | Drug Info | [2] | ||
| 2 | Mercaptopurine | Drug Info | [1] | ||
| 3 | Thioguanine | Drug Info | [1] | ||
| 4 | GRL-0667 | Drug Info | [3] | ||
| 5 | PMID20527968-compound-6577871 | Drug Info | [3] | ||
| 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 | Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020 Mar;19(3):149-150. | ||||
| 3 | Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biologic... J Med Chem. 2010 Jul 8;53(13):4968-79. | ||||
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