The compound, shown in gray, was calculated to bind to the SARS-CoV-2 spike protein, shown in cyan, to prevent it from docking to the Human Angiotensin-Converting Enzyme 2, or ACE2, receptor, shown in purple. Credit: Micholas Smith/Oak Ridge National Laboratory, U.S. Dept. of Energy

“We were able to design a thorough computational model based on information that has only recently been published in the literature on this virus,” Micholas Smith said, referring to a study published in Science China Life Sciences.

After being granted computational time on Summit through a Director’s Discretionary allocation, Micholas Smith used a chemical simulations code to perform molecular dynamics simulations, which analyze the movements of atoms and particles in the protein. He simulated different compounds docking to the S-protein spike of the coronavirus to determine if any of them might prevent the spike from sticking to human cells.

“Using Summit, we ranked these compounds based on a set of criteria related to how likely they were to bind to the S-protein spike,” Micholas Smith said.

The team found 77 small-molecule compounds, such as medications and natural compounds, that they suspect may be of value for experimental testing. In the simulations, the compounds bind to regions of the spike that are important for entry into the human cell, and therefore might interfere with the infection process.

After a highly accurate S-protein model was released in Science, the team plans to rapidly run the computational study again with the new version of the S-protein. This may change the ranking of the chemicals likely to be of most use. The researchers emphasized the necessity of testing of the 77 compounds experimentally before any determinations can be made about their usability.

“Summit was needed to rapidly get the simulation results we needed. It took us a day or two whereas it would have taken months on a normal computer,” said Jeremy Smith. “Our results don’t mean that we have found a cure or treatment for the Wuhan coronavirus. We are very hopeful, though, that our computational findings will both inform future studies and provide a framework that experimentalists will use to further investigate these compounds. Only then will we know whether any of them exhibit the characteristics needed to mitigate this virus.”

Computation must be followed by experiment. Computational screening essentially “shines the light” on promising candidates for experimental studies, which are essential for verifying that certain chemicals will combat the virus, according to Jeremy Smith. The use of a supercomputer such as Summit was important to get the results quickly.

This research was funded by the Laboratory Directed Research and Development program and used resources of the OLCF, a DOE Office of Science User Facility located at ORNL.

UT-Battelle manages Oak Ridge National Laboratory for DOE’s Office of Science, the single largest supporter of basic research in the physical sciences in the United States. DOE’s Office of Science is working to address some of the most pressing challenges of our time. For more information, visit https://energy.gov/science. – Rachel Harken

See ORNL’s main COVID-19 news site for more information on the laboratory’s fight against the novel coronavirus.