Novel Compounds Combat Viruses by Disrupting Their Envelope Structures
Researchers explored seven different peptoids with the aim of targeting virus membranes rather than their proteins. This innovative approach could usher in a new era of antiviral drugs. The development of antiviral therapies is a formidable task due to the rapid mutation rate of viruses, often leading to drug resistance. Unlike conventional treatments that target viral proteins on their surfaces, viruses' membrane structures are being considered as an alternative target. This is motivated by the fact that viruses can alter their protein properties through evolution, reducing the effectiveness of such treatments. A prime example was observed with the emergence of SARS-CoV-2 variants that managed to evade both drugs and vaccines designed for the original virus.
Viruses are enclosed by membranes composed of different molecules compared to the viral core. These membranes utilize lipids from the host cell to form their protective layer. An important lipid, phosphatidylserine, typically resides on the inner side of human cells, but it's found on the exterior of viruses. This unique positioning makes phosphatidylserine an attractive target for peptoids, which can be designed to recognize the lipid on virus membranes without affecting our own cells.
The research team tested seven peptoids against four different viruses. Notably, peptoids successfully disrupted the membranes of enveloped viruses such as Zika, Rift Valley fever, and chikungunya, while having no impact on coxsackievirus B3, which lacks a membrane. Interestingly, the susceptibility of the chikungunya virus to peptoids was correlated with the levels of phosphatidylserine in its membrane. In contrast, peptoids didn't show disruptive effects on membranes composed mainly of a different lipid called phosphatidylcholine. This underscores the significance of phosphatidylserine in the antiviral mechanism of peptoids.
The researchers are now actively engaged in pre-clinical studies to further assess the potential of these peptoids in combatting viruses and preventing the development of drug resistance. This approach holds promise not only for difficult-to-treat viruses like Ebola, SARS-CoV-2, and herpes, which have challenging membrane structures, but also as a novel strategy against other viral infections. The research team is also working towards the commercialization of these compounds, with the ultimate goal of translating their findings into tangible benefits for human health through clinical applications.
