resistant test will thus provide to clinicians important information for the management of HCV infection and for the individual tailoring of antiretroviral therapy. In this direction, a better knowledge of the extend of genetic variability among genotypes could assist the identification of RAMs with higher probability of development in that particular setting, highlighting patients with a higher risk of failure. Hepatitis C is a treatment-resistant disease with over 200 million people infected worldwide. Over 80 of infected patients develop chronic hepatitis. The HCV genome is a single-stranded RNA molecule with positive order Darapladib polarity that is,9,600 nucleotides in length. After infection of the host cell and liberation of the RNA genome from the protecting virus particle, the viral RNA is translated into a Dolutegravir multi-domain polyprotein that is proteolytically cleaved into ten products. The structural proteins are then used to assemble new virus particles, while the non-structural proteins participate in the replication of the viral genome. In the course of RNA replication, the viral genome is used as a template for the synthesis of negative-strand RNA, which next acts as a template for the production of positive-strand RNA. Replication is catalyzed by the NS3 helicase and the NS5B RNA-dependent RNA polymerase. The helicase represents the C-terminal portion of the NS3 protein. The NS3 helicase unwinds in an ATP-dependent manner doublestranded RNA into single strands. The chymotrypsin-like NS3 serine proteinase represents the N-terminal portion of the NS3 protein. NS3/4A cleaves the viral polyprotein precursor at the NS3/NS4A, NS4A/NS4B, NS4B/NS5A and NS5A/NS5B junction regions. The individual NS3 proteinase domain, however, is inactive. For cleavage activity in vitro and in vivo, the NS3 domain requires the NS4A co-factor. NS4A is a 54 residue amphipathic protein, with a hydrophobic Nterminus and a hydrophilic C-terminus. When complexed with NS4A, the NS3/4A domain is rearranged leading to the proper alignment of His-57, Asp-81, and Ser-139 of the catalytic triad. NS3/4A exhibits a Zn-binding site that serves a structural role and that is coded by the three Cys residues and His-149. The NS3/4A active site is positioned between two bbarrel domains and in a shallow g
