While there are now a slew of approved, effective vaccines that curb COVID-19 infections, there is only one FDA-approved therapeutic to fight ongoing COVID-19 infection: remdesivir. This relative lack of medications for COVID-19 patients has left researchers hunting for alternatives, ideally from known pharmaceutical compounds for easy deployment. Now, researchers at the San Diego Supercomputer Center (SDSC) are using HPC to continue the hunt – specifically, through one of SARS-CoV-2’s key proteins.

“The SARS-CoV-2 genome encompasses 29 proteins, including non-structural proteins (NSPs), and our study looked at one of these known as NSP15,” explained Igor Tsigelny, an SDSC researcher in structural biology, molecular modeling and bioinformatics, in an interview with SDSC’s Kimberly Mann Bruch. “NSP15 plays a critical role in both viral infection and replication, so we aimed to simulate how we could re-purpose FDA-approved compounds to fight this resilient protein.”

The researchers turned to SDSC’s Expanse supercomputer for the work, using molecular dynamics simulations to explore the FDA-approved compounds’ abilities to bind to NSP15. Expanse delivers 5.16 peak petaflops via 728 AMD Epyc 7742-powered compute nodes, 52 Nvidia V100-powered GPU nodes, and four large-memory nodes with 2TB of memory each. In total, the system boasts 208 GPUs, nearly 240TB of memory and over 93,000 compute cores.

After conducting the molecular dynamics simulations, the researchers identified 170 compounds of interest that show promise for inhibiting NSP15 on the SARS-CoV-2 virus. 21 of those compounds were further identified as “antiviral compounds that inhibited a wide range of viruses[.]”

“After examining these drugs, we became especially interested in a few that are currently used to treat viruses like HIV and hepatitis,” explained Kouznetsova, a project scientist at SDSC’s Center for Advanced Computational Science and Engineering. “We also simulated how a compound that is used to treat leukemia might also react to the NSP15 found in COVID-19.”

Now, those results are being used to guide further testing in the real world. To learn more about this research, read the coverage from SDSC’s Kimberly Mann Bruch here.

About the research

The research discussed in this article was published as “Potential SARS-CoV-2 Nonstructural Protein 15 Inhibitors: Repurposing FDA-Approved Drugs” in the October 2021 issue of the Journal of Exploratory Research in Pharmacology. It was written by Jason Y. Tang, Igor F. Tsigelny, Jerry P. Greenberg, Mark A. Miller and Valentina L. Kouznetsova. To read the article, click here.