Researchers at the Department of Energy’s Oak Ridge National Laboratory have used Summit, a supercomputer, to identify 77 small-molecule drug compounds that might warrant further study in the fight against the SARS-CoV-2 coronavirus, which is responsible for the COVID-19 disease outbreak.
The two researchers performed simulations on Summit of more than 8,000 compounds to screen for those that are most likely to bind to the main “spike” protein of the coronavirus, rendering it unable to infect host cells. They ranked compounds of interest that could have value in experimental studies of the virus. They published their results on ChemRxiv.
The idea was born out of an interest in the coronavirus’ entry point into a host cell. When Chinese researchers sequenced the virus, they discovered that it infects the body by one of the same mechanisms as the Severe Acute Respiratory Syndrome, or SARS, virus that spread to 26 countries during the SARS epidemic in 2003. The similarity between the two virus structures facilitated the study of the new virus.
After being granted computational time on Summit, the researchers used a chemical simulations code to perform molecular dynamics simulations, which analyze the movements of atoms and particles in the protein. They 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.
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.
