Correlation of OAS1 gene polymorphism at exon 7 splice accepter site with interferon-based therapy of HCV infection in Pakistan.

The most useful treatment for HCV infection worldwide is peg-interferon plus ribavirin, although the response varies from person to person. Hence, host genetics are significantly involved in the treatment response to HCV infection. The 2'-5' oligoadenylate synthetase (OAS) is one of the most important components of the immune system having significant antiviral functions. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP) at the exon 7 splice acceptor site (SAS) of OAS1 to interferon-based therapy of HCV infection. OAS1 genotyping was performed in 140 HCV patients by restriction fragment length polymorphism polymerase chain reaction method (RFLP-PCR). These patients were enrolled for the study in 2010-2013. OAS1 SNP was also established in 120 healthy controls. Correlation of HCV genotypes, OAS1 SNP, and other factors with response to interferon therapy were statistically analyzed by SPSS 13 software. There were no significant differences in the distribution of OAS1 genotypes between healthy and patients subjects. The distribution of AG and AA genotypes of OAS1 genotypes between sustained virological responders (SVRs) and the non-responders (NRs) group were also comparable. However, Pearson chi square analysis indicated that the patients possessing a GG genotype of the OAS1 gene at exon 7 SAS demonstrated significantly positive association with treatment response to HCV infection (p=0.039). This study determined that SNP at exon 7 SAS of OAS1 was significantly associated with response to interferon-based therapy of HCV infection in our population.

Current and future therapies for hepatitis C virus infection: from viral proteins to host targets.

Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects.