Target General Infomation
Target ID
T56518
Former ID
TTDR00970
Target Name
DNA polymerase/reverse transcriptase
Gene Name
P
Synonyms
HBV reverse transcriptase; Hepatitis B Virus reverse transcriptase; P
Target Type
Successful
Disease HBV infection [ICD9: 070.2-070.3; ICD10: B16, B18.0, B18.1]
Hepatitis virus infection [ICD9: 573.3; ICD10: K75.9]
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.
BioChemical Class
DNA-directed DNA polymerase
UniProt ID
Sequence
EHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGISRVSWPKFAVPNLQSLT
NLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLIGSSGLSRYVARLSSNSRINNNQYGTMQ
NLHDSCSRQLYVSLMLLYKTYGWKLHLYSHPIVLGFRKIPMGVGLSPFLLAQFTSAICSV
VRRAFPHCLAFSYMDDVVLGAKSVQHRESLYTAVTNFLLSLGIHLNPNKTKRWGYSLNFM
GYII
Drugs and Mode of Action
Drug(s) Entecavir Drug Info Approved HBV infection [536361]
Clevudine Drug Info Phase 3 HBV infection [549741]
LB80380 Drug Info Phase 2b HBV infection [551083]
MIV-210 Drug Info Phase 2 HBV infection [551136]
Pradefovir Drug Info Phase 2 Hepatitis virus infection [521736]
Inhibitor Clevudine Drug Info [549741]
LB80380 Drug Info [551083]
Modulator Entecavir Drug Info [532700]
MIV-210 Drug Info
Pradefovir Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
DRM DRM Info
References
Ref 521736ClinicalTrials.gov (NCT00230503) Dose-Ranging Study of Pradefovir in Patients With Compensated Hepatitis B. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 5497412011 Pipeline of Bukwang.
Ref 5510832011 Pipeline of LG Life Sciences.
Ref 551136Clinical pipeline report, company report or official report of Medivir (2011).
Ref 532700Effect of hepatitis B virus reverse transcriptase variations on entecavir treatment response. J Infect Dis. 2014 Sep 1;210(5):701-7.
Ref 5497412011 Pipeline of Bukwang.
Ref 5510832011 Pipeline of LG Life Sciences.

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