A promising antiviral inside the Hepatitis C Virus

A study published on January 5^th in the Biophysics journal reveals that a peptide derived from the Hepatitis C virus (HCV) kills a number of viruses while leaving the hosts cells unharmed by differentiating between the molecular make up of their membrane. The peptide was found to be highly effective against a range of cholesterol-containing viruses including West Nile, dengue, measles and HIV virus.

It is a known fact that HCV α-helical (AH) peptide has a broad range of anti-viral properties. This is the property that allows the peptide to hijack the host cell structures for HCV replication and it also produces ruptures in the viral membranes, exposing the viral genome to host enzyme that further destroy the pathogens.

Due to the lack of knowledge on why the AH peptide selectively attacks the viral envelope and leaves the host cell unharmed, there has been a road block in the development of therapies which exploits this property.

Keeping this in mind, senior study author Atul Parikh of the University of California, Davis and Nanyang Technological University, Singapore says “Although there are many antiviral drugs on the market, a common problem is that the virus learns how to evade them, becoming resistant to the drug treatment. There is a growing recognition that new classes of antiviral drugs that target multiple viruses are needed. Because the HCV-derived peptide appears to meet this need, we reason it targets the Achilles’ heel of viruses–a lipid coating or membrane envelope less likely to become resistant to drugs targeting them”.

In order to address this problem, a team of researchers led by Parikh and Nam-Cho of Nanyang Technological university tested the AH peptide on simple lipid membranes that varied in size and chemical composition.

It was seen that the virus-like models which were rich in cholesterol membranes showed molecular changes and increase in openings when they were exposed to the peptide. But at comparable concentrations the peptide did not cause any disturbance to the cholesterol-free vesicles. This made the researchers believe that a broad spectrum anti–viral activity was displayed by the AH peptide because it targets membranes rich in cholesterol which is shared by many viruses.

Further experimentation suggested that the AH peptide discriminates between viral envelopes and the host cell membrane based on size differences. According to Cho, “These results are important not only for furthering the membrane-targeting strategy for developing antivirals against HCV using viral peptides, but also for identifying other viruses, whose membrane compositions include comparable concentrations of cholesterol, that can be inhibited by the HCV antiviral. Although several compounds that destabilize the viral membrane have been recently proposed, no drug on the market currently targets the lipid membrane.”

Before researchers can translate this promising strategy to humans, much work is needed to expand these studies to more realistic model systems. The researchers plan to continue biophysical investigations with membrane compositions that closely match either viral or cellular membranes.

“Understanding how the drug candidate interacts with these biologically important lipids, we reason, should open the door to deciphering the rich and complex biology of these systems and lead to new opportunities for antiviral strategies,” Parikh says. “Studies such as ours provide hope that replacing the old paradigm of ‘one-bug, one-drug’ with broadly applicable drugs against which viruses cannot develop resistance may become a reality soon.