Exploiting new potential targets for anti-hepatitis B virus drugs.
Based on the recent studies of HBV strains with different replication efficiency, several new potential targets for anti-HBV replication have been presented. These include the viral and cellular regulatory factors associated with HBV replication and the process for encapsidation of viral genome and budding into endoplasmic reticulum (ER). A putative regulatory domain has been reported at the carboxyl-end of reverse transcriptase (RT) and when serine is substituted for proline at residue 652 of RT, replication efficiency of HBV is decreased. Substitution of proline for threonine at the 2798 nucleotide of the terminal protein (TP) gene, renders the mutant completely replication deficient. Expression of TP blocks the interferon (IFN) pathway and inhibits the responsive state of cells to interferons ( IFN) alpha and gamma. Interference of HBV capsid assembly drastically affects the encapsidation of viral genome, a crucial process for reverse transcription and viral DNA synthesis. Small molecules (bis-ANS) have been reported to act as a "wedge" to misdirect the polymerization of capsid, resulting in inhibition of virus replication. Another new group of compounds (HAP) has been shown to inhibit virus replication and also inhibit the assembly of viral capsid (core particle). Finally the capsids containing HBV genome are enveloped by budding into endoplasmic reticulum and release from virus infected cells, and this morphogenesis and secretion of HBV is dependent on glucosidases in the ER of host cells. Competitive inhibition of these glucosidases has been suggested as strategy against HBV replication.
Wen
Y-M
YM
Department of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China. ymwen@shmu.edu.cn
Lin
X
X
Ma
Z-M
ZM
D000998:Antiviral Agents / Q000494:pharmacology*; D002213:Capsid / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000502:physiology; D015195:Drug Design; D015684:Gene Products, pol / Q000737:chemistry / Q000502:physiology; D006515:Hepatitis B virus / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000502:physiology; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D000998:Antiviral Agents; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D014759:Viral Envelope Proteins; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase