Scientists have identified a set of small molecules that can block the activity of a key protein in SARS-CoV-2 that causes COVID-19, a finding that provides a promising path for new therapeutics for the disease.
The team of researchers at the University of Georgia (UGA) in the US noted that the SARS-CoV-2 protein PLpro is essential for the replication and the ability of the virus to suppress host immune function.
The compounds, naphthalene-based PLpro inhibitors, are shown to be effective at halting SARS-CoV-2 PLpro activity as well as replication, according to the research published in the journal ACS Infectious Diseases.
The researchers explored inhibitors designed to knock out PLpro and stop replication of the virus.
They 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.
“Obviously now we see the current coronavirus is probably going to be with us for a while — if not this one, then probably other types of coronaviruses,” said Scott Pegan, a professor at UGA.
“These compounds are a good starting point for therapeutic development. They have all the properties you would typically want to find in a drug, and they have a history of not being considered toxic,” he said.
The compounds offer a potential rapid development path to generating PLpro-targeted therapeutics for use against SARS-CoV-2, the researchers said.
“The kind of small molecules that we’re developing are some of the first that are specifically designed for this coronavirus protease,” Pegan said.
“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,” he said.
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