MacMillan, Ploss labs to map viral-host interactions for COVID-19

Thursday, Apr 30, 2020

By Wendy Plump, Department of Chemistry

Responding to a challenge that tragic necessity has thrown to countless research labs around the world, a team from the Princeton Department of Chemistry will deploy its new cell mapping technology to shed light on the molecular interplay between COVID-19 and its host. The team is collaborating with Princeton molecular biologists who study viruses.

A tool called µMap, announced just two months ago by the MacMillan Group, is the basis for a research project to reveal how human proteins communicate with viral particles on a cell surface, interactions that drive a multitude of health outcomes for the host. The group hopes this “proximity labeling” system will provide valuable data to scientists trying to understand the coronavirus infection cycle as they race to develop drug therapies.

As a starting point, the group will zero in on the tiny spikes protruding from the virus particle. It is believed that a unique folding action at the tip of the spikes allows COVID-19 to tightly attach to a cell via a receptor called ACE2, or, angiotensin converting enzyme-2. But, is this the only molecule required for the virus to enter cells?

“Everyone believes that the spike binds with this protein called ACE2. We want to figure out where else it’s going. No one knows. It’s clear there should be other receptors. But right now, there’s no way of figuring out what those are, and no one has any guesses,” said Jacob Geri, a postdoctoral research fellow with the MacMillan Group. “Our µMap technology is uniquely poised to answer that question.”

Or, as third-year graduate student Beryl Li put it, “You first have to know what to target before you figure out how to target.”

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