Mimic the body’s defenses to destroy enveloped viruses

2023-08-04 15:45:01

Just as bacteria can develop resistance to antibiotics, viruses can also evade drug treatments. It is difficult to develop therapies against these microorganisms, because the viruses usually mutate or hide inside cells.

However, despite this difficulty with viruses, an antiviral therapy with peptides has been developed that mimics the way the immune system deals with viruses and, in three laboratory tests, has been able to deactivate three viruses of effective way

You could say that viruses are like biological “zombies”. They are not fully alive, nor are they inert, and can only multiply within a host, such as the cells of our body. Often the immune system naturally destroys pathogens with specific molecules, such as antibodies.

Some lesser-known components of the immune system’s defenses are small protein-like molecules called antimicrobial peptides. However, these peptides are not good candidates for drugs, as they are expensive to manufacture, are quickly cleared from the body, and can cause side effects. Instead, the authors of the new study have been able to mimic its function using laboratory molecules called peptoids, which are not easily destroyed by the body and are less expensive to produce. Previously, Annelise Barron’s team (Stanford University in the United States) had shown that certain peptoids could cross and destroy the SARS-CoV-2 and herpes viruses. This time, together with Kent Kirshenbaum and Patrick M. Tate (both from New York University, United States) and their colleagues, they have sought to determine whether peptoids can inactivate three other membrane-encapsulated “enveloped” viruses—the virus Zika, Rift Valley fever, and chikungunya—as well as coxsackie B3, which lacks a membrane. There are currently no treatments for infections caused by these microorganisms.

Photograph captured by electron microscope and then processed showing Zika virus particles, shown in red. (Image: Cynthia Goldsmith/CDC)

In these experiments, three of the linear peptoids previously studied by Barron’s team were used, as well as four newly released versions with increased antiviral activity.

The researchers created models of virus membranes using common lipids, including phosphatidylserine (PS).

Membranes were more effectively destroyed when PS was present at higher concentrations, suggesting that the peptoids specifically target PS.

Although both human and viral membranes contain lipids, their distribution is different in each case, allowing an antiviral agent to target the invader rather than the host.

Next, the team incubated the peptoids with whole particles of the infectious virus. Again, each performed differently against the three enveloped viruses: some destroyed all three, others just one. However, none of the peptoids were able to inactivate non-enveloped coxsackie virus B3, demonstrating that the mechanism of action depends on the presence of the viral envelope.

The researchers say that understanding this mechanism could help design future peptoid-based antiviral treatments.

The study is titled “Peptidomimetic Oligomers Targeting Membrane Phosphatidylserine Exhibit Broad Antiviral Activity”. And it has been published in the academic journal ACS Infectious Diseases. (Source: American Chemical Society)