We often hear how bad it is to have high cholesterol, but what that cholesterol was the only way to kill a virus? Researchers have successfully used a peptide derived from the hepatitis C virus (HCV) to take down a broad range of viruses, including West Nile, measles, dengue, and HIV — all of which contain cholesterol. It was this characteristic that enabled the peptide to discriminate between viruses and host cells, leaving the latter unharmed. "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," said senior study author Atul Parikh, of the University of California, Davis and Nanyang Technological University, Singapore, in a press release. "There is a growing recognition that new classes of antiviral drugs 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." Researchers have known for a while now that the HCV a-helical (AH) peptide possesses antiviral properties, provided those very properties are what allow the peptide to hijack host cell structures for HCV replication. This property also gives the peptide the ability to rip into viral membranes, making the viral genome vulnerable to host enzymes that destroy pathogens. Development of AH centered therapies has been limited, however, by the lack of knowledge surrounding why, exactly, it only attacks vir We often hear how bad it is to have high cholesterol, but what that cholesterol was the only way to kill a virus? Researchers have successfully used a peptide derived from the hepatitis C virus (HCV) to take down a broad range of viruses, including West Nile, measles, dengue, and HIV — all of which contain cholesterol. It was this characteristic that enabled the peptide to discriminate between viruses and host cells, leaving the latter unharmed. "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," said senior study author Atul Parikh, of the University of California, Davis and Nanyang Technological University, Singapore, in a press release. "There is a growing recognition that new classes of antiviral drugs 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." Researchers have known for a while now that the HCV a-helical (AH) peptide posesses antiviral properties, provided those very properties are what allow the peptide to hijack host cell structures for HCV replication. This property also gives the peptide the ability to rip into viral membranes, making the viral genome vulnerable to host enzymes that destroy pathogens. Development of AH centered therapies has been limited, however, by the lack of knowledge surrounding why, exactly, it only attacks viral envelopes. In hopes of answering this question, a team of scientists led by Parikh and Nam-Joon Cho, also of Nanyang Technical University, tested the AH peptide on a simplified model of lipid membranes — each varied in chemical composition and size. The results were promising: Virus-like models with cholesterol-rich membranes showed molecular changes and an increase in openings, while cholesterol-free vesicles of comparable concentrations continued unperturbed. The researchers believe targeting cholesterol-rich membranes is most likely why the AH peptide is able to display such broad-spectrum antiviral activity. Through further experimenting, they found the peptide discriminated between these viruses and their host cell membranes based on size. "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," Cho said. "Although several compounds that destabilize the viral membrane have been recently proposed, no drug on the market currently targets the lipid membrane." A step in the right direction, yes, but there is still a lot of work to be done before this strategy can be translated to humans. "These simplified model membranes are excellent models to dissect how drugs target lipid components of viral or cell membranes, but we need to remember that they are still models," Cho said. "It will be important to extend the cues drawn from these studies to biological systems, namely human cells and live viruses[;]to validate the biophysical insights before preclinical translation can occur." Parikh added that an understanding of how the peptide reacts within biologically important lipids could open the door to new opportunities for antiviral strategies, and that broadly applicable drugs capable of acting against many viruses (without them becoming resistant) may soon be a reality. Source
