• Previous research has shown SARS-CoV-2 causes an infection in a person by entering the body and binding its spike proteins to ACE2 receptors on a cell’s surface.
• Researchers have designed peptides that resemble the ACE2 receptors targeted by the viral spike proteins.
• These peptides “trick” the virus into binding with them instead of a cell, potentially inactivating the virus before it can trigger infection.
• Researchers hope to create nasal sprays or surface treatments from these peptides that will reduce or block SARS-CoV-2 before infection can occur.

There have been approximately 28 million COVID-19 cases reported in the United States, with over 500,000 deaths from the disease. And although vaccination programs are in full operation to curb the spread, there is still an urgent need for other ways to prevent COVID-19.

For SARS-CoV-2 to trigger an infection in someone, it must enter the body and attach to ACE2 receptors on cells. These receptors appear throughout the body, including the vascular system, nose and throat, and the brain, with abundant expression in the lungs and small intestines.

The process of infecting cells begins when SARS-CoV-2 enters the body through the nose or mouth. When inside the body, the virus uses its outer spike protein to attach itself to ACE2 receptors on the surface of cells. Once bound to the receptor, the virus begins to fuse into the cell and release its genetic material, instructing the host cell to make new viruses.

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SARS-CoV-2 is very proficient at this process due to its ability to bond tightly to ACE2 receptors through its spike proteins.

If the immune system does not catch this dangerous activity quickly and attack, SARS-CoV-2 can continue to replicate and destroy cells. Like most pathogens, the combination of cell disruption and damage initiated by the virus and the immune system’s reaction to the invader is what causes the symptoms of COVID-19.

Because preventing COVID-19 is more advantageous than treating the disease, finding a way to stop SARS-CoV-2 from binding to cells is crucial.

Researchers from The Ohio State University may have discovered a way to interrupt this infection process in or outside of the body, which could slow or inactivate the virus. Their research appears in the journal Bioconjugate Chemistry.

Using peptides to ‘fool’ SARS-CoV-2

Co-lead authors Amit Sharma, assistant professor of veterinary biosciences at Ohio State, and Ross Larue, research assistant professor of pharmaceutics and pharmacology, also at Ohio State, along with their colleagues, looked at peptides as a way to inhibit SARS-Cov-2 from attaching to cells.

Sharma explains:

“Our goal is that any time SARS-CoV-2 comes into contact with the peptides, it will inactivate the virus. This is because the virus spike protein is already bound to something that it needs to use to bind to the cell. To do this, we have to get to the virus while it is still outside the cell.”

Using new technology in crystallizing proteins and microscopy, the team examined images of SARS-CoV-2 and ACE2 receptors, looking specifically at the virus’s spike protein and the point of attachment on ACE2.

After noticing a spiral-like tail on ACE2 receptors, the scientists focused on testing several peptides to see if any would incite the SARS-CoV-2 spike protein to attach and subsequently reduce the virus’s ability to replicate in cell cultures.

They were particularly interested in creating the shortest possible peptides that could bind to spike proteins using the minimum number of contact points.

Compared to controls, the team found that two peptides, one with minimum contact points and another with larger points of contact, effectively reduced the virus’s ability to infect cells in a culture.

This finding is significant because when SARS-CoV-2 attaches to a peptide, it can no longer bind to a cell and replicate.

What are the implications of this discovery?

Because these peptides can potentially bind with the virus and inactivate it or reduce its ability to trigger infections, this newly discovered technology may open a new pathway in the fight against COVID-19.

Product development could include manufacturing peptide-based nasal sprays that block SARS-CoV-2 as it enters the body or creating aerosol sprays that inactivate the virus when applied to surfaces.

Larue says that, with the results they have achieved with peptides, he feels the team is now in a position to move towards product development.

Regarding the researcher’s future plans with their discovery, Sharma says:

“The goal is to neutralize the virus effectively and potently, and now, because of the emergence of variants, we are interested in assessing our technology against the emerging mutations.”

Sharma and Larue are currently the inventors of this technology, with a provisional patent application pending.

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