In January 2020, as the first COVID-19 cases were appearing in the United States, David Frick and his students already had begun investigating the virus behind them. They studied the group of proteins that allows the virus to multiply inside a cell.
Frick, a chemistry professor in the College of Letters & Science, has devoted most of his research career to creating antiviral drugs. He’s also one of thousands of researchers who spent the past year exploring drug compounds with the potential to halt the pandemic. Several compounds that Frick developed six or seven years ago to test on other viruses are showing promise.
“This work began years ago when we were testing our compounds on the hepatitis C virus,” Frick says. “Whether any existing drugs will work, however, really just depends on how they fit the structure of the COVID-19 proteins.”
He began by comparing the replication proteins in SARS-CoV-2, the virus that causes COVID-19, to those in the coronavirus that caused the less-severe SARS outbreak in 2003. Frick and his lab colleagues identified the protein most distinct from its earlier cousin, as well as the protein most similar. He then started testing hundreds of druglike compounds – some of which he developed – to see if any interfered with those proteins.
The team found that the protein most different from the 2003 coronavirus can add or remove a component in human proteins called ADP ribose, which is often how pathogens cause disease. These are called “epigenetic” modifications, and some of Frick’s compounds seek to disrupt that process.
Frick is taking a different approach with the protein that’s most similar. That protein, called a helicase, is necessary for most viruses to read instructions encoded in genes. Frick has years of experience developing helicase blockers – compounds that can stop a virus from accessing its genetic command center.
For this research, he is receiving help from Wilfred Tysoe, distinguished professor of chemistry, and Nicholas Silvaggi, associate professor of chemistry. Tysoe’s lab members are using computer models to simulate how compounds interact with the COVID-19 proteins on the molecular level. Silvaggi’s lab is mapping the proteins’ atomic structure using X-rays so researchers can visualize and simulate how some compounds might bind to the helicase.
As of early 2021, remdesivir was the lone drug approved to treat COVID-19. But previous research suggests that more successful viral therapies consist of a “cocktail” of antivirals that’s less likely to produce drug resistance. It underscores the need for more antiviral candidates. Frick’s team has identified several compounds with potential, but more work is needed to fully understand how they act on infected cells.