Hepatitis C virus proteins as targets for drug development: the role of bioinformatics and modelling.
Hepatitis C virus (HCV), a member of the Flaviviridae family, has been recognised to be responsible for both parenterally transmitted and sporadic non-A and non-B hepatitis affecting 1-3% of the world population. HCV is a positive stranded RNA virus encoding a single polyprotein which contains at least ten unique structural and non-structural proteins. Amongst these the structural protein E2 has been of special interest for vaccine development and the serine protease NS3, which is responsible for cleavage of the polyprotein, for the development of small molecule inhibitors. We will focus on the contribution of computational techniques and the use of structural information for the design and discovery of novel therapeutic agents for these targets. Both drug discovery and vaccine design efforts will be discussed taking into account also the problem of emerging resistance.
Lahm
A
A
Istituto di Ricerche di Biologia Molecolare P. Angeletti, Pomezia, Italy.
Yagnik
A
A
Tramontano
A
A
Koch
U
U
D019295:Computational Biology / Q000379:methods; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D014761:Viral Hepatitis Vaccines / Q000276:immunology* / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000737:chemistry; D014764:Viral Proteins / Q000096:biosynthesis*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D003545:Cysteine; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase