Target Information
Target General Information | Top | |||||
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Target ID |
T56518
(Former ID: TTDR00970)
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Target Name |
Hepatitis B virus Reverse transcriptase (HBV RT)
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Synonyms |
P; HBV reverse transcriptase
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Gene Name |
HBV RT
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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, theRC- 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 | ||||||
EC Number |
EC 2.7.7.49
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Sequence |
EHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGISRVSWPKFAVPNLQSLT
NLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLIGSSGLSRYVARLSSNSRINNNQYGTMQ NLHDSCSRQLYVSLMLLYKTYGWKLHLYSHPIVLGFRKIPMGVGLSPFLLAQFTSAICSV VRRAFPHCLAFSYMDDVVLGAKSVQHRESLYTAVTNFLLSLGIHLNPNKTKRWGYSLNFM GYII Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Adefovir Dipivoxil | Drug Info | Approved | Hepatitis B virus infection | [2] | |
2 | Entecavir | Drug Info | Approved | Hepatitis B virus infection | [3] | |
Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | Clevudine | Drug Info | Phase 3 | Hepatitis B virus infection | [4] | |
2 | LB80380 | Drug Info | Phase 2b | Hepatitis B virus infection | [5] | |
3 | MIV-210 | Drug Info | Phase 2 | Hepatitis B virus infection | [6] | |
4 | Pradefovir | Drug Info | Phase 2 | Hepatitis virus infection | [7] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 4 Modulator drugs | + | ||||
1 | Adefovir Dipivoxil | Drug Info | [8] | |||
2 | Entecavir | Drug Info | [1] | |||
3 | MIV-210 | Drug Info | [9] | |||
4 | Pradefovir | Drug Info | [10] | |||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | Clevudine | Drug Info | [4] | |||
2 | LB80380 | Drug Info | [5] |
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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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 |
Target Profiles in Patients | Top | |||||
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Drug Resistance Mutation (DRM) |
References | Top | |||||
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REF 1 | Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response. J Infect Dis. 2014 Sep 1;210(5):701-7. | |||||
REF 2 | Telbivudine: a new option for the treatment of chronic hepatitis B. Expert Opin Biol Ther. 2007 May;7(5):751-61. | |||||
REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 4 | 2011 Pipeline of Bukwang. | |||||
REF 5 | 2011 Pipeline of LG Life Sciences. | |||||
REF 6 | Clinical pipeline report, company report or official report of Medivir (2011). | |||||
REF 7 | ClinicalTrials.gov (NCT00230503) Dose-Ranging Study of Pradefovir in Patients With Compensated Hepatitis B. U.S. National Institutes of Health. | |||||
REF 8 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
REF 9 | Emerging antivirals for the treatment of hepatitis B | |||||
REF 10 | DOI: 10.1128/AAC.01566-05 |
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