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Know Your Enemy

Understanding the life cycle of the hepatitis C virus (HCV) – how it replicates and how it interacts with the host’s body – gives researchers insight into leveraging weak links where this virus could be best battled.

Researchers have long known that the virus itself is an enveloped, positive-stranded RNA virus in the same family of viruses as those causing dengue fever and West Nile disease. All positive-stranded RNA viruses rely on the same sneaky MO: they change the cytoplasmic membrane of a person’s cells so that there is an isolated microenvironment where the virus can hide itself away to replicate. Clearly, this method of the hepatitis C virus has been successful since an estimated 130-170 million people worldwide have a chronic infection of HCV.

Efforts to develop a vaccine have not yet produced an effective one. The genetic diversity and rapid mutation rate of the hepatitis C virus serves as potentially insurmountable challenges.

As the search for weaknesses in the HCV progressed, one of the major breakthroughs came with the development of direct-acting antivirals (such as boceprevir and telaprevir), which target sites called NS3-4A and NS5B. These direct-acting antivirals bind to the protease enzyme sites and prevent the virus from producing proteins needed in the HCV life cycle. Direct-acting antivirals brought much higher cure rates with greatly shortened treatment times than ever before.

Other potential weak links of HCV, which could be exploited by disease-curing medications, include: the tendency for HCV to bind to LDL cholesterol, the way in which HCV breaches the liver cell’s plasma membrane proteins, HCV RNA replication, ways to boost the host’s resistance to viral replication, and targeting the HCV assembly and secretion pathways. Currently, the most clinically advanced host-targeted agents are cyclosporin A analogs which appear to block interaction between CYPA and HCV NS5A protein.

The more we learn about hepatitis C, the more we can target this virus to effectively prevent and treat this terrible disease with the least collateral damage to the patient.

BioPlus Specialty Pharmacy

Eyre NS, Helbig KJ, Beard MR. Current and future targets of antiviral therapy in the hepatitis C virus life cycle. Future Virology 2014;9(11):947-965.

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