Hepatitis C--virology and future antiviral targets.
The hepatitis C virus is a single-stranded RNA virus with a genome approximately 9,000 nucleotides in length. The genome consists of a single, large open reading frame (ORF) and 5' and 3' untranslated regions. The highly conserved 5' untranslated region is 341 nucleotides in length with a complex secondary structure and may function as an internal ribosomal entry site (IRES). The 3' untranslated region is approximately 500 nucleotides in length and contains a hypervariable region, followed by a poly(U) sequence and a highly conserved 98-nucleotide element with a stable secondary structure. The ORF codes form a single polyprotein that is processed into as many as 10 polypeptides, including a capsid protein (core), two envelope proteins (E1 and E2), and nonstructural proteins (NS2, NS3, NS4, and NS5). Potentially suitable antiviral targets include the IRES, protease, helicase, and RNA polymerase. In vitro studies show that antisense oligonucleotides can inhibit the production of structural HCV proteins and may be therapeutically useful if the problems of stability and delivery can be solved. The binding of HCV envelope proteins to CD81, a potential receptor for viral entry into hepatocytes, has recently been described and also raises the possibility of agents to block the binding to CD81 or the entry of the virus into cells.
Di Bisceglie
A M
AM
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63104, USA.
D000998:Antiviral Agents / Q000627:therapeutic use*; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D014779:Virus Replication
D000998:Antiviral Agents