Antimicrobial Peptoids Inactivate Enveloped Viruses in Lab Tests

Scientists have made significant progress in combating viral infections by developing a novel antiviral therapy inspired by the immune system's natural defense mechanism. In a study reported in ACS Infectious Diseases, a team including scientists from Stanford, Loyola, and NYU successfully created a peptoid therapy that effectively inactivated three different viruses in laboratory tests. The approach involves targeting specific lipids in the viral membranes, disrupting their functions and rendering them harmless.

Viruses, often likened to biological zombies, exist in a peculiar state between living and non-living entities. They can only multiply within a host, such as human body cells, making them challenging to treat with conventional drugs. Typically, the immune system combats these pathogens with specialized molecules, such as antibodies, to neutralize the threat. However, less well-known members of the immune system's defense force are small protein-like molecules called antimicrobial peptides, which possess potent antiviral properties.

To mimic the function of antimicrobial peptides, the team turned to lab-made molecules called peptoids, which offer several advantages over natural peptides. Peptoids are more cost-effective to produce and are less likely to be rapidly eliminated from the body, making them suitable candidates for therapeutic development. Previous studies by co-author Annelise Barron's team demonstrated that certain peptoids were effective in piercing and destroying the SARS-CoV-2 and herpes viruses. Building on this success, the researchers, in collaboration with senior author Kent Kirshenbaum and colleagues, aimed to investigate the peptoids' potential against additional viruses, including Zika, Rift Valley fever, chikungunya, and coxsackie B3, for which no current treatments exist.

The researchers employed both linear and circularized versions of the peptoids in their experiments, with the latter showing increased antiviral activity. The team created model virus membranes using common lipids, including phosphatidylserine (PS), and found that membranes were most effectively disrupted when PS was present in higher concentrations. This discovery suggests that the peptoids target PS specifically, leading to viral inactivation. Notably, while both human and viral membranes contain PS, they are distributed differently in each case, allowing the peptoids to selectively attack the viral membranes without affecting host cells.

During the investigation, the team incubated the peptoids with whole, infectious virus particles. The results showed that the peptoids worked to varying extents on the three enveloped viruses (Zika, Rift Valley fever, and chikungunya. However, none of the peptoids could neutralize the non-enveloped coxsackie B3 virus, indicating that the mechanism of action hinges on the presence of the viral envelope.

The researchers' findings hold promise for the development of future peptoid-based antiviral treatments. Understanding the mechanism of action behind the peptoid therapy could pave the way for the design of more effective antiviral drugs, offering a potential solution against emerging viral threats.