RESISTANT viruses may soon face a potent new antiviral body in the form of the amphipathic α-helical (AH) peptide, a molecule found within the hepatitis C virus that is able to analyse and discriminate between viral and host cells.
“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 Prof Atul Parikh, Department of Biomedical Engineering, University of California, Davis, California, USA. In a breakthrough study on the AH peptide, the mechanisms behind the molecule’s known antiviral capacity have been revealed.
Essentially, the AH peptide can act as a mediator of both viral attack and host defence, as it can rupture the membrane of a virus and expose the viral DNA, enabling an attack on the virus by host cell enzymes. The latter ability makes the peptide an attractive candidate for drug development, so Prof Parikh and his team set out to investigate exactly how the AH peptide is able to selectively function.
The membrane of a virus is largely comprised of non-protein hydrocarbon molecules called lipids. Common lipids include fats, oils, vitamins, and crucially in this context, cholesterol. Using simple virus-like models, research indicated that cholesterol-rich membranes were most vulnerable to the AH peptide; the membrane chemistry was altered and its physiology damaged. Moreover, it became clear that the peptide discerns viral from host cell membranes by detecting differences in their size and composition.
The simple model used in this study requires far more development before the AH peptide reaches the clinical realm. For one, the effects of the peptide have yet to be observed within in vivo biological systems. Refined modelling of viral and host membranes will offer a more realistic view of the peptide’s potential for drug development. “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” said Prof Parikh.
It is hoped that the AH peptide (and other viral peptides) will aid the fight against viruses with cholesterol-rich membranes such as West Nile, dengue, measles, and the human immunodeficiency virus (HIV).