Disabling COVID’s ‘key’ to create long-term treatment

Disarming the virus that causes COVID-19 until it’s no worse than the common cold is a powerful strategy researchers are using to attack the disease.

As COVID-19 mutates, VCU College of Engineering’s Michael Peters, Ph.D. is accelerating efforts to disable the “spikes” that give the coronavirus particle its familiar shape — and its power to prey on cells. 

Peters, a professor of chemical and life science engineering, has watched the behavior of the SARS-CoV-2 spike protein like a detective tracking a suspect at large. With the emergence of new variants, the criminal gets craftier. 

The virus uses the spike protein to latch on to human epithelial cells that line the lungs and vasculature. Peters likens this process to a burglar trying to break into a house. The surface of the spike protein — or “key” — is composed of subunits called protomers. Each protomer is in an “up” or “down” state. Think of these states as grooves on the key: The “up” state appears to allow binding, while the “down” state is believed to be relatively inactive. Therefore, forcing protomers into a “down” state may be a step toward future treatments.

“With the original strain, the key didn't fit very well, so it had to jiggle and turn a couple of times before opening the door,” Peters explains. “New variants are more problematic, because, through the multitude of mutations that result from infection and replication, the virus has stumbled onto a better key.” 

Peters urges people not to wait for a COVID treatment, however, which he said is risky and far in the future. “They can mitigate this virus now by getting vaccinated,” he said.

Last year, VCU Innovation Gateway launched the COVID-19 Innovation Center, an online portal dedicated to research around the virus. Peters, a regular collaborator with the Innovation Gateway team, placed his invention on the site. The work caught the attention of Hoth Therapeutics Inc., a clinical-stage biopharmaceutical company based in New York that develops therapeutics for, among other conditions, asthma, chronic wounds, psoriasis and acne. And now, COVID-19.

Within a matter of weeks an exclusive licensing deal emerged, Innovation Gateway director of licensing, Magdalena K. Morgan says. Under the agreement, Hoth is able to check Peters’ therapies against the virus and its variants. The relationship has prompted two rounds of Hoth funding to continue Peters’ research.

“Hoth really wanted to jump on the research,” Morgan says. “It really was one of the quickest licensing deals we’ve ever done.”