Washington State University researchers have identified a way to block viruses from entering cells by targeting a specific protein interaction, according to findings published in the journal Nanoscale. The research focused on herpes viruses and involved collaboration between the School of Mechanical and Materials Engineering and the Department of Veterinary Microbiology and Pathology.
Jin Liu, corresponding author and professor in the School of Mechanical and Materials Engineering, explained, "Viruses are very smart. The whole process of invading cells is very complex, and there are a lot of interactions. Not all of the interactions are equally important - most of them may just be background noise, but there are some critical interactions."
The team investigated a fusion protein used by herpes viruses to enter host cells. Understanding how this protein operates has been challenging, which contributes to the lack of vaccines for these types of viruses.
Professors Prashanta Dutta and Jin Liu utilized artificial intelligence and molecular-scale simulations to examine thousands of potential amino acid interactions within the protein. They developed an algorithm that could distinguish between background interactions and those that play a crucial role in virus entry.
Under Anthony Nicola’s leadership from the Department of Veterinary Microbiology and Pathology, researchers mutated one key amino acid identified by their analysis. This mutation significantly reduced the virus's ability to fuse with—and thus enter—cells.
Liu emphasized the importance of computational methods in their approach: "It was just a single interaction from thousands of interactions. If we don't do the simulation and instead did this work by trial and error, it could have taken years to find," he said. "The combination of theoretical computational work with the experiments is so efficient and can accelerate the discovery of these important biological interactions."
While blocking this interaction proved effective at stopping viral entry in experiments, researchers do not yet fully understand how changes at this small scale affect larger structural changes in the fusion protein. Liu noted ongoing efforts: "There is a gap between what the experimentalists see and what we can see in the simulation. The next step is how this small interaction affects the structural change at larger scales. That is also very challenging for us."
PhD students Ryan Odstrcil, Albina Makio, and McKenna Hull also contributed to this project, which received funding from the National Institutes of Health.
