By Julia Munemo
Assistant Professor of Chemistry Bob Rawle recently published a paper that corrects some misunderstandings about how the West Nile Virus operates and creates a pathway for further research that could lead to the development of an anti-viral drug in the future. Chemistry majors Olivia Graceffa ’22 and Abe Park ’22 contributed to his research and co-authored the paper, published in the November issue of the American Chemical Society’s Infectious Disease journal.
Before joining the Williams faculty in 2018, Rawle, a biophysical chemist, was a postdoctoral fellow in a joint research collaboration between Stanford University and the University of Virginia. At Stanford, he used a computer model developed to understand West Nile Virus to study a virus from the same family—Zika Virus. Viruses in this family are transmitted by mosquitos and can cause everything from mild symptoms to severe illness.
“I found, and fixed, some fundamental flaws in the model that had been developed,” Rawle says about his work with Zika. “Once I got to Williams, I wanted to see if those same fixes could be applied to the model to better understand the virus it had originally been designed for, West Nile.”
Park joined his lab in the summer of 2019, and Graceffa the following summer. They ran models to figure out if the flaw Rawle had uncovered about Zika also pertained to West Nile—it did. Then they determined that Rawle’s fix lined up with data about West Nile.
For a virus to infect a cell, it first must bind to a molecule on that cell, then get swallowed up and rip a hole through which it can inject its genetic material directly into the cell’s interior. The process, called molecular fusion, is linear for many viruses—first there’s step A, then B, then C, then D.
“But we had seen with Zika Virus that the data couldn’t be explained by a linear process,” says Rawle, who teaches courses in chemistry and biophysical chemistry as well as a course for nonmajors called AIDS: The Disease and Search for a Cure. “That means it has what’s called an off-pathway state.”
Imagine the virus going through step A and B but then getting sidetracked. “Something else happens, unrelated to molecular fusion,” Rawle says. If left alone, steps C and D will eventually take place. Rawle says it’s exciting to discover that West Nile Virus has such an off-pathway state, because “that is a clear target for a drug. If you can stabilize the off-pathway state, you have effectively inhibited the virus from infecting the cell.”
He’s quick to add that he isn’t conducting research into drug development. “Our job was to determine if an off-pathway state exists,” he says. “Subsequent research will be about the nature of that off-pathway state and ways to stabilize it.”
Rawle is grateful for the help he received from Graceffa and Park, adding: “Abe and Olivia’s exceptional work was foundational to the success of this project—their contributions brought this work to light. The project has also been a tremendous opportunity for their own development as scientists.”
Julia Munemo is a contributing writer for Williams Magazine.