Peptoid Oligomers Target Viral Membranes

Researchers at New York University have developed a new method to target many viruses that cause disease. For viruses with a lipid membrane, which includes many that commonly cause disease, this new technique could prove to be fatal. By targeting the lipid membrane, the approach may circumvent the treatment resistance that arises when viruses mutate to alter their surface proteins, which are the most common targets for conventional anti-viral drugs. This new approach is based on a synthetic version of antimicrobial peptides, which are naturally produced by our immune system and can target pathogens such as bacteria and viruses. These researchers have developed a more stable synthetic version that they call “peptoids” that can more effectively bind to viral envelope lipids, disrupting the viral membrane and destroying the viral particle.

While it may seem morbid to frame it as such, the clock is ticking until the next viral pandemic. In the calm before the next storm, developing new anti-viral treatments is crucial so that we will be better prepared. However, viruses are a worthy adversary, rapidly mutating their surface proteins so that the drug targets that are present now will likely change relatively soon. This has been a key limitation with many anti-viral strategies which target these surface proteins. For instance, we can see how fast SARS-CoV-2 mutated to create new variants with different properties and different levels of susceptibility to vaccine-mediated immunity.

However, one component of viruses does not even originate with the viral genome itself, but rather directly from our own cells. This is the viral membrane, which many viruses ‘steal’ from our own cells as they force our cellular machinery to create new viral particles. While such theft is deplorable, it renders the virus vulnerable to treatments that target the membrane, and does not allow the virus to develop an effective resistance strategy, since it does not generate the membranes itself.

This latest technology targets the viral membrane, and it uses antimicrobial peptides naturally produced by our own immune system as inspiration. Such peptides can effectively target viruses, but they are relatively unstable and could cause side-effects if delivered in large doses. Instead, these researchers designed a synthetic version called “peptoids”, which are more stable and more specific for viral membranes.

So far, the peptoids have shown efficacy in targeting viruses such as Zika, Rift Valley fever, and chikungunya. Moreover, the peptiods should not target our own cells, as the viral membrane is a little different in its composition from our own membranes. “Because phosphatidylserine is found on the exterior of viruses, it can be a specific target for peptoids to recognize viruses, but not recognize—and therefore spare—our own cells,” said Patrick Tate, a researcher involved in the study. “Moreover, because viruses acquire lipids from the host rather than encoding from their own genomes, they have better potential to avoid antiviral resistance.”

See a video below that illustrates the peptoid mechanism of action.