NS5A--from obscurity to new target for HCV therapy.
The hepatitis C virus (HCV) non-structural 5A (NS5A) protein is essential for viral RNA replication and may play a role in subverting host intracellular signaling pathways. Although no intrinsic enzymatic activity has been ascribed to NS5A, this proline-rich hydrophilic phosphoprotein is likely to exert its functions by interacting with viral and cellular factors. Recent studies using the HCV replicon cell culture system as a model for HCV RNA replication as well as for high-throughput screening of pharmacological inhibitors have revealed blockade of NS5A as a promising therapeutic strategy for the treatment of HCV. This review will summarize our progress in understanding the role of NS5A in HCV RNA replication and will introduce the most recent patents on inhibitors of NS5A.
Schmitz
Uli
U
Genelabs Technologies, Inc., 505 Penobscot Drive, Redwood City, CA 94063, USA. ulis@genelabs.com
Tan
Seng-Lai
SL
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D015195:Drug Design; D024882:Drug Resistance, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D010330:Patents as Topic; D011487:Protein Conformation; D012367:RNA, Viral / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase