Target Information
Target General Information | Top | |||||
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Target ID |
T71501
(Former ID: TTDS00309)
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Target Name |
Hepatitis B virus Polymerase (HBV P)
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Synonyms |
Protein P
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Gene Name |
HBV P
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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 |
Multifunctional enzyme that converts the viral RNA genome into dsDNA in viral cytoplasmic capsids. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3'- to 5'-endonucleasic mode. Neo-synthesized pregenomic RNA (pgRNA) are encapsidated together with the P protein, and reverse-transcribed inside the nucleocapsid. Initiation of reverse-transcription occurs first by binding the epsilon loop on the pgRNA genome, and is initiated by protein priming, thereby the 5'-end of (-)DNA is covalently linked to P protein. Partial (+)DNA is synthesized from the (-)DNA template and generates the relaxed circular DNA (RC-DNA) genome. After budding and infection, the RC-DNA migrates in the nucleus, and is converted into a plasmid-like covalently closed circular DNA (cccDNA). The activity of P protein does not seem to be necessary for cccDNA generation, and is presumably released from (+)DNA by host nuclear DNA repair machinery.
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BioChemical Class |
DNA-directed DNA polymerase
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UniProt ID | ||||||
Sequence |
MPLSYQHFRKLLLLDDGTGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFT
GLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTVNEKRRLQLIMPARFYPKVT KYLPLDKGIKPYYPEHLVNHYFQTRHYLHTLWKAGILYKRETTHSASFCGSPYSWEQDLQ HGAESIHQQSSGILSRPPVGSSLQSKHRKSRLGLQSQQGHLARRQQGRSWSIRAGFHPTA RRPFGVEPSGSGHTTNFASKSASCLHQSPVRKAAYPSVSTFEKHSSSGHAVELHNLPPNS ARSKSERPVFPCWWLQFRNSKPCSDYCLSLIVNLREDWGPCDDHGEHHIRIPRTPARVRG GVFLVDKNPHNTAESRLVVDFSQFSRGNYRVSWPKFAVPNLPSLTNLLSSNLSWLSLDVS AAFYHIPLHPAAMPHLLVGSSGLSRYVARLSSNSRYFNNQHGTMQNLHDSCSRNLYVSLL LLYQTFGRKLHLYSHPIILGFRKIPMAVGLSPFLLAQFTSAICSVVRRAFPHCLGFSYMD DVVLGAKSVQHRESLYTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYIIGSWGTLPQDHI VQKIKHCFRKLPVNRPIDWKVWQRIVGLLGFAAPFTQCGYPALMPLYACIQAKQAFTFSP TYKAFLSKQYMNLYPVARQRPGLCQVFADATPTGWGLA Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Telbivudine | Drug Info | Approved | Hepatitis B virus infection | [2] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | ATI-2173 | Drug Info | Phase 2 | Hepatitis B | [3] | |
2 | NCO-48 | Drug Info | Phase 1 | Hepatitis B virus infection | [4] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | Valtorcitabine | Drug Info | Discontinued in Phase 2 | Hepatitis virus infection | [5] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 4 Inhibitor drugs | + | ||||
1 | Telbivudine | Drug Info | [1] | |||
2 | ATI-2173 | Drug Info | [6] | |||
3 | NCO-48 | Drug Info | [7] | |||
4 | Valtorcitabine | Drug Info | [8] |
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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There is no similarity protein (E value < 0.005) for this target
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Co-Targets | Top | |||||
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Co-Targets |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Nucleos(t)ide analogues for hepatitis B virus: strategies for long-term success. Best Pract Res Clin Gastroenterol. 2008;22(6):1081-92. | |||||
REF 2 | Nucleoside and nucleotide analogs in the treatment of chronic hepatitis B. Enferm Infecc Microbiol Clin. 2008 May;26 Suppl 7:32-8. | |||||
REF 3 | ClinicalTrials.gov (NCT04847440) A Study of Safety and Efficacy of ATI-2173 in Combination With Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B Virus Infection and in Subjects With Hepatitis D Virus Coinfection. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT04629976) Activity of NCO-48 Fumarate in Treatment-Naive Adults With Chronic Hepatitis B. U.S. National Institutes of Health. | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013710) | |||||
REF 6 | ATI-2173, a Novel Liver-Targeted Non-Chain-Terminating Nucleotide for Hepatitis B Virus Cure Regimens. Antimicrob Agents Chemother. 2020 Aug 20;64(9):e00836-20. | |||||
REF 7 | Safety, Tolerability and Pharmacokinetics of NCO-48 Fumarate in Healthy Subjects | |||||
REF 8 | Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting. J Pharm Sci. 2008 Mar;97(3):1109-34. |
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