You can’t catch COVID-19 in virtual reality, but you can certainly help beat it! Dr. Kovalevsky and his team at Oak Ridge National Laboratory (ORNL), are combining neutron crystallography and VR to create accurate 3D models of SARS-CoV-2 main protease (Mpro), the enzyme that allows the coronavirus to reproduce.
High resolution VR models of Mpro allow scientists to virtually build and test newly designed compounds to determine how well they can bind to the catalytic site on the enzyme surface. This data helps the scientific community design novel drugs that inhibit Mpro.
SARS-CoV-2 main protease is an indispensable protein enzyme that enables the coronavirus to reproduce. During the process of replication, a polyprotein chain is synthesized and the main protease cleaves this chain in multiple sites, releasing functional proteins. Inhibiting the protease is vital to stopping the virus from spreading in patients with COVID-19.
Given its biological importance, Mpro was identified as a target for drug development early in the pandemic. Scientists modeled the 3D architecture of Mpro and studied the structure of its catalytic site to design molecules that will block the protease’s activity. Thousands of such studies have already been conducted.
Designing Inhibitors in VR
Up till now, most studies of Mpro have been based on cryogenically preserved crystals. However, the team at ORNL approached the problem differently by also solving room temperature and neutron structures, which provide a much more detailed picture of the enzyme.
Dr. Kovalevsky and his team use virtual reality as their method of choice to visually analyze these complex structures and perform virtual reality-assisted small molecule design. Their approach led to the discovery of a novel chemical structure that acts as a non-covalent inhibitor of the main protease:
“This novel chemical structure is different than what has been previously studied by the global community and could open new avenues of research with exciting possibilities for combating SARS-CoV-2,” says first author Dr. Kneller and “I would have never come up with that [chemical modification] if we didn't go through VR and look at it.”
Dr. Kovalevsky routinely uses Nanome to analyze molecular structures, test ideas, and optimize the design of small molecule compounds. Read our full case study to learn how Nanome supports Dr. Kovalevsky’s research.