In the neverending human-vs-virus battle, scientists often focus on disrupting the protein coating on the bugs. New research shows a different way forward: using certain compounds to act as molecular "pins" that pop the membranes holding viruses together. The research could open the door to a new class of broad-spectrum antiviral treatments.
Viruses are covered in proteins that act as keys to unlock access to our cells. For this reason, a lot of research has gone into figuring out how to disrupt these proteins. If we can mangle the keys enough, the thinking goes, then the bugs won't be able to get inside our cells, reproduce, and begin the chain of infection that can have catastrophic results on our health. One issue with this approach, however, is that it tends to be a one-cure-for-one-virus approach. And if the virus mutates, and changes its outer layer of proteins as we've seen with COVID, then the treatment might be rendered less effective.
However, beneath the layer of proteins on many viruses is a membrane surrounding the germ's genetic material. Researchers at New York University (NYU) have now figured out a way to break this membrane and cause the viruses to die. Because a lot of viruses have membranes, the finding could lead to antivirals that work on a broad range of germs.
"We found an Achilles heel of many viruses: their bubble-like membranes," said Kent Kirshenbaum, professor of chemistry at NYU and the study’s senior author. "Exploiting this vulnerability and disrupting the membrane is a promising mechanism of action for developing new antivirals."
To do just that, the research team turned to the antimicrobial peptides that are produced by our immune system when it encounters a bacterial, viral, or fungal invasion. These peptides work by disrupting the membranous layer contained in many viruses. While the peptides are a natural part of our immune system, they have proven to be too easily broken down by our innate biology when synthesized in the lab to fight viruses. They can also be toxic to healthy cells.
You say peptide, I say peptoid
With these limitations in mind, the team investigated seven peptoids instead. These are engineered compounds that are molecularly very similar to peptides, but harder for the body to break down.
In the study, the researchers pitted the peptoids against three viruses known to have membranes: those that cause Zika, Rift Valley fever, and chikungunya. They also tried them against the virus that causes coxsackievirus B3, which lacks a membrane. The tests showed that the peptides were effective in popping the membrane on all of the viruses that possessed one, in effect shutting them down. As expected, the peptoids were not effective on the virus lacking a membrane.
Inside out
The success the peptoids had at destroying the membranous viruses was due to their ability to target a lipid known as phosphatidylserine, which some viruses harvest from our own cells to create their enveloping membrane. Phosphatidylserine is protected deep inside our cells, yet it's exposed on the outer membranes of viruses. For this reason, the peptoids were able to target the viruses while sparing healthy cells.
The researchers are now continuing pre-clinical studies to further understand the role peptoids could play in combating a wider-range of viruses that could include Ebola, SARS-CoV-2, and herpes.
"There is an urgent need for antiviral agents that act in new ways to inactivate viruses," said Kirshenbaum. "Ideally, new antivirals won’t be specific to one virus or protein, so they will be ready to treat new viruses that emerge without delay and will be able to overcome the development of resistance."
"We need to develop this next generation of drugs now and have them on the shelves in order to be ready for the next pandemic threat – and there will be another one, for sure," he added.
The research has been published in the journal, ACS Infectious Diseases.
Source: New York University
