Researchers from Ohio State University have found a way to trick the coronavirus disease 2019 (COVID-19) into binding to a false ACE2 receptor so it can’t infect cells. The findings were published in the journal Bioconjugate chemistry.
“Our goal is that every time SARS-CoV-2 comes in contact with peptides, the virus is inactivated. This is because the Spike virus is already bound to something that needs to be used to bind to a cell,” Amit Sharma said. , co-leader of the study and assistant professor of veterinary biosciences in the state of Ohio. “To do that, we have to get to the virus while it’s still out of the cell.”
Because the SARS-CoV-2 virus uses ACE2, a receptor protein on the surface of a target cell found in the lungs and nasal cavity, as an access point for infection, researchers wondered if it would be able to develop a replica in which the virus would bind to the real one. COVID-19 binds extremely tightly to ACE2, which is one of the reasons the disease is so contagious.
To do this, the team reviewed images of the spike protein SARS-CoV-2 and ACE2 receptors, observing exactly how they interact with each other and what it takes to solidify in place. They found a small tail like a ribbon that looked like a focal point of attachment.
They then tested various protein fragments, called peptides, to determine which of them safely bind to the COVID-19 spike protein, as well as the ability to prevent or reduce virus replication within cell cultures. They found that 2 peptides, one with a large contact point and one with minimal points, could do so.
“Most of the peptides we designed are based on the tape that contacts Spike,” Sharma said. “We focused on creating the shortest possible peptides with minimal essential contacts.”
These discoveries are the beginning of a product development process that will be continued by other virologists and pharmaceutical chemists to try to develop them and find ways to apply them in the fight against disease.
“We take a multilateral approach,” Sharma said. “With these peptides, we have identified the minimum contacts required for virus inactivation. In the future, we plan to focus on developing aspects of this technology for therapeutic purposes.”