title: Current drug discovery strategies for treatment of hepatitis C virus infection.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection represents a major worldwide-health problem. The current standard of care is combination therapy with pegylated interferon and ribavirin, which achieves a successful response in only approximately 40% of genotype I patients.
  
  
  RESULTS
  The biology of HCV infection has been under intensive research and important progress has been made in understanding the replication cycle of the virus. Several therapeutic targets have been under investigation, such as NS3 protease, NS4A replicase and NS5B polymerase. New potential targets, such as NS2 protease, as well as CD-81 and claudin-1 entry co-receptors, have also been identified.
  
  
  CONCLUSIONS
  Clinical evaluations of drug candidates targeting NS3 protease, NS4A cofactor, and NS5B polymerase have demonstrated the potential of developing small molecules that interfere with the replication of the virus. Additional issues, including genotype coverage, resistant mutations, and combination therapy represent major challenges for future drug discovery efforts.
authors.affiliation: Merck Research Laboratories, Kenilworth, NJ, USA. kccheng101@gmail.com
authors.forename: K-C
authors.initials: KC
authors.lastname: Cheng
authors.forename: Samir
authors.initials: S
authors.lastname: Gupta
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.forename: Annette S
authors.initials: AS
authors.lastname: Uss
authors.forename: George F
authors.initials: GF
authors.lastname: Njoroge
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D015195:Drug Design; D055808:Drug Discovery; D006207:Half-Life; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase