Target Information
Target General Information | Top | |||||
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Target ID |
T03896
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Target Name |
Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A)
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Synonyms |
HCV Hepacivirin/NS4A; HCV NS3P/NS4A; HCV p70/NS4A
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Gene Name |
HCV NS3/4A
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
Function |
Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).
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UniProt ID | ||||||
Sequence |
APITAYAQQTRGLLGCIITSLTGRDKNQVEGEVQIVSTAAQTFLATCINGVCWTVYHGAG
TRTIASPKGPVIQMYTNVDQDLVGWPAPQGSRSLTPCTCGSSDLYLVTRHADVIPVRRRG DSRGSLLSPRPISYLKGSSGGPLLCPAGHAVGIFRAAVCTRGVAKAVDFIPVENLETTMR SPVFTDNSSPPVVPQSFQVAHLHAPTGSGKSTKVPAAYAAQGYKVLVLNPSVAATLGFGA YMSKAHGIDPNIRTGVRTITTGSPITYSTYGKFLADGGCSGGAYDIIICDECHSTDATSI LGIGTVLDQAETAGARLVVLATATPPGSVTVPHPNIEEVALSTTGEIPFYGKAIPLEVIK GGRHLIFCHSKKKCDELAAKLVALGINAVAYYRGLDVSVIPTSGDVVVVATDALMTGYTG DFDSVIDCNTCVTQTVDFSLDPTFTIETITLPQDAVSRTQRRGRTGRGKPGIYRFVAPGE RPSGMFDSSVLCECYDAGCAWYELTPAETTVRLRAYMNTPGLPVCQDHLEFWEGVFTGLT HIDAHFLSQTKQSGENLPYLVAYQATVCARAQAPPPSWDQMWKCLIRLKPTLHGPTPLLY RLGAVQNEITLTHPVTKYIMTCMSADLEVVTSTWVLVGGVLAALAAYCLSTGCVVIVGRV VLSGKPAIIPDREVLYREFDEMEEC Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
1 | BOCEPREVIR | Drug Info | Approved | Hepatitis C virus infection | [2], [3] | |
2 | Glecaprevir; pibrentasvir | Drug Info | Approved | Hepatitis C virus infection | [4] | |
3 | Simeprevir | Drug Info | Approved | Chronic HCV-1 infection | [5], [6] | |
4 | Sofosbuvir + velpatasvir + voxilaprevir | Drug Info | Approved | Hepatitis C virus infection | [4] | |
5 | Telaprevir | Drug Info | Approved | Hepatitis C virus infection | [3], [7] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 3 Modulator drugs | + | ||||
1 | BOCEPREVIR | Drug Info | [3] | |||
2 | Simeprevir | Drug Info | [1] | |||
3 | Telaprevir | Drug Info | [3] | |||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Glecaprevir; pibrentasvir | Drug Info | [4] | |||
2 | Sofosbuvir + velpatasvir + voxilaprevir | Drug Info | [4] |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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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 | Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651. | |||||
REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7876). | |||||
REF 3 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
REF 4 | 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85. | |||||
REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7367). | |||||
REF 6 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7871). |
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