Synthetic molecules can burst virus membranes

Viruses can mutate quickly. This impedes efforts to develop lasting antiviral therapies. A study led by Kent Kirshenbaum at New York University overcomes this constraint by targeting the virus membrane.

When the body is invaded by pathogens, the immediate immune response is to produce antimicrobial peptides (AMPs). Kirshenbaum’s team synthesized novel compounds that mimic the structure and function of AMPs. They called these peptide-like molecules peptoids (ACS Infect. Dis. 2023, DOI: 10.1021/acsinfecdis.3c00063).

Using AMPs against viruses isn’t new, but scientists haven’t successfully managed to use these large, difficult-to-manufacture molecules as drugs.

Kirshenbaum’s team was inspired by Stanford University bioengineer Annelise E. Barron’s earlier work showing how peptoids mimicked AMPs. After researchers made the previously linear molecules cyclic, they expected to see good antiviral activity. But they were surprised to find that the molecules were active against all the enveloped viruses they tested, including those that cause Zika, chikungunya, and Rift Valley fever.

Kirshenbaum says the peptoids were found to be targeting a lipid called phosphatidylserine, which is believed to be in the membrane of all enveloped viruses.

Biotech company Maxwell Biosciences (Kirshenbaum is its chief scientific officer) is seeking approval from the US FDA to use the peptoids in preclinical studies.

William C. Wimley, a biochemist and molecular biologist at Tulane University who was not involved in the study, says this paper confirms that broad spectrum antivirals could target the viral envelope and that phosphatidylserine is a key lipid to target. But he also says it is unclear from the paper if the compounds will be relevant to drug development.

The researchers say, however, that their so-far unpublished data from golden Syrian hamsters demonstrate therapeutic and prophylactic activity against SARS-CoV-2, the virus that causes COVID-19.