Nav: Home

Inside the hepatitis C virus is a promising antiviral

January 05, 2016

A peptide derived from the hepatitis C virus (HCV) kills a broad range of viruses while leaving host cells unharmed by discriminating between the molecular make-up of their membranes, reveals a study published January 5 in the Biophysical Journal. The peptide was potent against a range of cholesterol-containing viruses, including West Nile, dengue, measles, and HIV.

"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," says senior study author Atul Parikh of the University of California, Davis and Nanyang Technological University, Singapore. "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."

It's been known that the HCV α-helical (AH) peptide has broad antiviral properties--the same property that allows the peptide to hijack host cell structures for HCV replication also produces ruptures in viral membranes, exposing the viral genome to host enzymes that destroy the pathogens. However, the development of therapies inspired by the actions of the AH peptide has been limited by the lack of knowledge about why it selectively attacks the viral envelope but not host cell membranes.

To address this question, a collaborative research team led by Parikh and Nam-Joon Cho of Nanyang Technological University tested the AH peptide on simplified model lipid membranes that varied in their size and chemical composition. Upon exposure to the peptide, virus-like models with cholesterol-rich membranes showed molecular changes and an increase in openings. But at comparable concentrations, the peptide did not perturb cholesterol-free vesicles.

The researchers believe that the AH peptide probably displays broad-spectrum antiviral activity because it targets cholesterol-rich membranes shared by many viruses (this evolutionary conservation is important because viruses would be slow to develop resistance to it). Additional experiments suggested that the AH peptide also discriminates between viral envelopes and host cell membranes on the basis of their size differences.

"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 says. "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. "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 says. "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."

To that end, the researchers plan to continue their biophysical investigations with membrane compositions that more closely match those of viral and cellular membranes. They will also investigate the effects of other viral peptides on these membranes and establish collaborations with virologists to begin to explore translational opportunities.

"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."
-end-
This work received support from the U.S. Department of Energy, the National Research Foundation, the National Medical Research Council, and Nanyang Technological University.

Biophysical Journal, Hanson and Gettel et al.: "Cholesterol-enriched microdomain formation induced by viral-encoded, membrane active amphipathic peptide."

The Biophysical Journal(BJ), published by Cell Press for the Biophysical Society, is a bimonthly journal that publishes original articles, letters, and reviews on the most important developments in modern biophysics--a broad and rapidly advancing field encompassing the study of biological structures and focusing on mechanisms at the molecular, cellular, and systems level through the concepts and methods of physics, chemistry, mathematics, engineering, and computational science. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Virus Articles:

Tracking the HI virus
A European research team led by Prof. Christian Eggeling from the Friedrich Schiller University Jena, the Leibniz Institute of Photonic Technology (Leibniz IPHT), and the University of Oxford has now succeeded in using high-resolution imaging to make visible to the millisecond how the HI virus spreads between living cells and which molecules it requires for this purpose.
Prior Zika virus or dengue virus infection does not affect secondary infections in monkeys
Previous infection with either Zika virus or dengue virus has no apparent effect on the clinical course of subsequent infection with the other virus, according to a study published August 1 in the open-access journal PLOS Pathogens by David O'Connor of the University of Wisconsin-Madison, and colleagues.
Smartphone virus scanner is not what you think
The current leading method to assess the presence of viruses and other biological markers of disease is effective but large and expensive.
Early dengue virus infection could "defuse" zika virus
The Zika virus outbreak in Latin America has affected over 60 million people up to now.
Catch a virus by its tail
At a glance: Research uncovers key mechanism that allows some of the deadliest human RNA viruses to orchestrate the precise copying of the individual pieces of their viral genome and replicate.
More Virus News and Virus Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...