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

Abstract

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.

Reduced frontal activation during verbal fluency task in chronic hepatitis C patients with interferon‐based therapy as measured by near‐infrared spectroscopy

“…Combination treatment with pegylated interferon‐α (PEG‐IFN) plus ribavirin (RBV) has been shown to be effective in treating patients with chronic hepatitis C (CHC) . In 2011, the directly acting antiviral agents, hepatitis C virus (HCV) non‐structural protein (NS)3/4 A serine protease inhibitors, were added to PEG‐IFN and RBV with increased efficacy . Recently, an NS5B inhibitor, sofosbuvir, has emerged as a potent agent with pangenotypic efficacy, resulting in the first IFN‐free regimen for the treatment of CHC.…”

“…However, they are linked with the development of resistance and viral breakthrough (IFN‐free regimen, such as NS5A inhibitor). The current standard‐of‐care treatment of CHC patients with the development of resistance is IFN‐based therapy . Despite its efficacy, one of the most common side‐effects of this regimen is depression.…”

Computational Screening of Flavonoids for HCV Inhibition

“…Having this evident medical requirement, extensive efforts have been disbursed to develop effectual preventive and therapeutic strategies for hepatitis C infection (Bartenschlager R et al, 2013). Until 2011, the combination of pegylated interferon (PegIFN) -α and ribavirin was the most standard treatment for chronic hepatitis C infection having a success rate of 40-50% (Imran M et al, 2013). This treatment has various side effects including flu-like symptoms, anxiety and haemolytic anaemia and other contra-indications that are not advisable to patients from receiving the drugs.…”

High-yield production of a chimeric glycoprotein based on permuted E1 and E2 HCV envelope ectodomains

“…HCV is a positive sense, single-stranded RNA virus belonging to the Hepacivirus genus of the Flaviviridae family. Currently, there is no vaccine for HCV and the antiviral therapy which is used include the use of polyethylene glycol-modified interferon, ribavirin and protease inhibitors although there are also other drugs in phase III of clinical development (Imran et al, 2014). Unfortunately, all the treatments are expensive and are not 100% effective (Feld and Hoofnagle, 2005).…”