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Discovery of Small Molecules That Block Coronavirus Offers Promising Path for COVID-19 Therapeutics

By HospiMedica International staff writers
Posted on 22 Jun 2020
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Image: Discovery of Small Molecules That Block Coronavirus Offers Promising Path for COVID-19 Therapeutics (Photo courtesy of Mark Sorrow)
Image: Discovery of Small Molecules That Block Coronavirus Offers Promising Path for COVID-19 Therapeutics (Photo courtesy of Mark Sorrow)
A set of drug-like small molecules can block the activity of a key SARS-CoV-2 protein, providing a promising path for new COVID-19 therapeutics.

Researchers at the University of Georgia (Athens, GA, USA) were the first to evaluate the SARS-CoV-2 protein PLpro, known to be essential in other coronaviruses for both its replication and its ability to suppress host immune function. They explored inhibitors designed to knock out PLpro and stop replication of the virus. The researchers began with a series of compounds that were discovered 12 years ago and shown to be effective against SARS, but development was cut short since SARS had not reappeared.

These compounds, naphthalene-based PLpro inhibitors, are shown to be effective at halting SARS-CoV-2 PLpro activity as well as replication. They offer a potential rapid development path to generating PLpro-targeted therapeutics for use against SARS-CoV-2. The researchers used modeling techniques to locate the differences between PLpro in the 2003 outbreak and the current outbreak, revealing the comparative weakness of the SARS-CoV-2 PLpro and suggesting potential inhibitors for testing.

“The kind of small molecules that we’re developing are some of the first that are specifically designed for this coronavirus protease,” said Scott Pegan, director of UGA’s Center for Drug Discovery and professor of pharmaceutical and biomedical sciences in the College of Pharmacy. “Up till now, most therapeutic work against SARS has targeted another virulence factor, C3Lpro. This is a great start with a different target. Our hope is that we can turn this into a starting point for creating a drug that we can get in front of the Food and Drug Administration.”

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