Scientists have put forward an approach to block a protein that the novel coronavirus uses. They cut and disable crucial components of the immune system. Using this, the virus will be unable to produce copies of itself.
The researchers from the University of Texas Health Science Center in the US developed two molecules that inhibit the molecular “scissor” enzyme used by the coronavirus called SARS-CoV-2-PLpro.
According to the study, published in the journal Science, SARS-CoV-2-PLpro promotes infection by sensing and processing viral and human proteins. “This enzyme executes a double-whammy,” said study senior author Shaun K. Olsen. He is also an associate professor of biochemistry and structural biology at UT Health San Antonio.
“It stimulates the release of proteins that are essential for the virus to replicate. It also inhibits molecules called cytokines and chemokines that signal the immune system to attack the infection,” Olsen said.
SARS-CoV-2-PLpro cuts human proteins ubiquitin and ISG15. These help maintain protein integrity by acting as a molecular scissor, he explained.
The scientists developed the inhibitors, which are very efficient at blocking the activity of SARS-CoV-2-PLpro. But they yet do not recognize other similar proteins in human cells.
“This is a critical point: The inhibitor is specific for this one viral enzyme and doesn’t cross-react with human enzymes with a similar function,” he said.
Further, the researchers said this specificity would be a key determinant of the therapeutic value of this particular approach.
When the scientists compared SARS-CoV-2-PLpro against similar enzymes from coronaviruses, they learned that it processes ubiquitin and ISG15 much differently than its counterpart.
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“One of the key questions is whether that accounts for some of the differences we see in how those viruses affect humans, if at all.”
By understanding the similarities and differences of these enzymes in various coronaviruses, the researchers said it may be possible to develop inhibitors that are effective against multiple viruses. Olsen said that these inhibitors can also be modified if other variants arrive.