The study suggests AH peptide - a molecule derived from the hepatitis C virus - could lead to an effective antiviral drug against viruses with cholesterol-rich membranes.
In a study published in the Biophysical Journal, the team shows how the molecule - called AH peptide - could have a powerful antiviral effect against viruses that have cholesterol-rich membranes, such as West Nile, dengue, measles and human immunodeficiency virus (HIV).
The researchers believe their findings could help discover new drugs that viruses will find it more difficult to resist.
Drug resistance is a growing problem with antiviral drugs, as senior author Atul Parikh, a professor in biomedical engineering who holds posts at the University of California-Davis and Nanyang Technological University in Singapore, explains:
"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."
Previous studies have already shown that the AH peptide derived from the hepatitis C virus (HCV) has broad antiviral properties. The new study takes this a step further by discovering how it distinguishes viruses from host cells.
The HCV-derived AH peptide targets cholesterol-rich lipid virus membranes. By attacking this "Achilles' heel" that is common to many viruses, the peptide meets a growing need for new types of antiviral that target multiple viruses, says Prof. Parikh.
AH peptide targets cholesterol-rich lipid membranes
In its natural state, the AH peptide helps HCV hijack host cells for virus replication. Previous studies have already shown that the peptide also has the ability to rupture the membrane of certain viruses, allowing host cell enzymes to kill them by attacking their exposed DNA.
Such a feature makes HCV AH-peptide an attractive starting point for drug development, but it was not possible to take it further because scientists could not work out how the peptide selectively targets the viral membrane but not that of host cells.
To address this question, Prof. Parikh and colleagues used a simple virus-like model of lipid membranes, where they could change their size and composition.
When they tested AH peptide against various lipid membrane models, they found those that were cholesterol-rich were the most susceptible - the peptide altered their chemistry and punched holes in them. Membranes without cholesterol did not succumb to this effect.
Many viruses have cholesterol-rich membranes, say the researchers, who conclude this is the feature that gives AH peptide such broad antiviral activity.
AH peptide distinguishes host membrane by size
In further experiments, the team also showed that AH peptide distinguishes between viral membranes and host cell membranes through size differences.
There is still a long way to go before AH peptide can be developed into a drug for clinical use. For example, the study used a simple model of virus membranes, so we do not yet know if AH peptide has the same effect in living biological systems with real viruses and host cells.
As a next step, the team plans to develop membrane models that are more like those of real viruses and host cells. They also want to see what happens when they test other viral peptides on these membranes.
Prof. Parikh says finding out how such compounds interact with these biologically important lipids helps us better understand their complex biology and opens the door to new developments in antiviral drugs. He concludes:
"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."
Meanwhile, Medical News Today recently learned that having hepatitis C may raise risk of Parkinson's. A study published in the journal Neurology describes how researchers in Taiwan found patients infected with hepatitis C virus were 30% more likely to develop Parkinson's disease than uninfected patients.