- A team of researchers from Ohio State University has developed tiny protein fragments that can block the novel coronavirus from infecting cells, and it could be turned into a potential COVID-19 treatment that can be administered by anyone.
- Much like neutralizing antibodies resulting from a coronavirus infection or vaccination, the peptides bind to the spike protein, preventing the virus from hooking up to ACE2 receptors and infecting cells.
- The peptides could be used to develop a nasal spray that would stop the virus from infecting cells in the nasal cavity and in the lungs, as well as other drugs that could block the virus’s spike protein.
The novel coronavirus vaccines authorized for emergency use right now have the same goal, and they work similarly, regardless of the underlying technology. Vaccines have to prevent severe COVID-19 and death, and Phase 3 trials have shown that various drugs can do that with various degrees of efficacy. But that means a vaccinated individual can still contract the virus. The coronavirus can still replicate inside the nose and attempt to bind to lung cells. But the vaccine will train the immune system to block the virus from infecting cells, which would reduce the pathogen’s ability to harm the body. The vaccines target the virus’s spike protein, teaching the immune system to mass-produce neutralizing antibodies that can prevent it from linking to ACE2 receptors on cells.
Vaccines can be adapted to deal with new mutations, as is the case with the flu vaccine that gets refreshed each year. But if this new nasal spray works as well as the researchers claim, there might be other ways of stopping the virus from doing damage to your body.
Ohio State University researchers studied the chemical bonds between the coronavirus and the ACE2 receptor that sits at the exterior of cells in the nose, lungs, and other organs to understand how the two “shake hands.” The coronavirus has to infect cells to survive. To do that, it binds to the ACE2 receptor and then takes over the chemical plant inside the cell to replicate itself. Its offspring leave the dying cell on a mission to infect other cells. This happens repeatedly until the immune system comes in to stop the virus and remove debris, including the dead cells.
After analyzing the coronavirus-ACE2 bond, the researchers came up with protein fragments called peptides that can appear to the virus to be a portion of the ACE2 receptor. These peptides would bind to the SARS-CoV-2 virus’ spike protein, blocking the virus from infecting cells. This process is similar to how neutralizing antibodies work. Antibodies are proteins the immune system manufactures after exposure to the virus or after vaccination. They will also inhibit the same spike protein. The difference between them is that the immune system will make more antibodies for months after the infection or vaccination, maybe years. The peptides would need to be applied to the respiratory system with the help of a nasal spray. But that might be enough to stop the virus from multiplying.
Preventing replication would reduce the viral load in an infected person. This would also reduce the risk of complications and death, and it could speed up recovery. Also, by reducing the viral load in the lungs and nose, this potential coronavirus treatment could reduce the likelihood that an infected person would transmit the disease to other people.
“Our goal is that any time SARS-CoV-2 comes into contact with the peptides, the virus will be inactivated. This is because the virus Spike protein is already bound to something that it needs to use in order to bind to the cell,” co-lead author of the study Amit Sharma said in a statement. “To do this, we have to get to the virus while it’s still outside the cell.”
Sharma and his team analyzed images of the coronavirus spike protein and the ACE2 receptor, zooming in on the regions where the two elements interact. After understanding the chemical connections, they focused on the spiral ribbon-like tail of the ACE2 receptor for designing the peptides.
“Most of the peptides we designed are based on the ribbon contacting the spike,” Sharma said. “We focused on creating the shortest possible peptides with the minimum essential contacts.”
The team tested several peptides in lab trials and discovered that two of the candidates effectively reduced infection compared to control groups. These peptides can be used to develop other substances that can neutralize the virus, not just COVID-19 treatments like nasal sprays. They could be built into aerosol surface disinfectants, which would neutralize the virus before it even reaches the human body.
Sharma and his team will now focus on developing aspects of their coronavirus inhibitors for therapeutic purposes. The researchers will also test their peptides against the emerging mutations of the virus. Clinical trials will be needed to validate the efficacy of this potential coronavirus treatment in humans before any related COVID-19 drugs can be made available to the general public.
The Ohio State University study can be seen in Bioconjugate Chemistry.
