Scientists have proposed an approach to block a protein that new coronoviruses use to cut and deactivate critical components of the immune system and to make copies of themselves, a breakthrough that COVID – can cause new drugs against 19.
Researchers, including the University of Texas at San Antonio Health Sciences Center (UT Health San Antonio) in the United States, have developed two molecules that inhibit the molecular “scissors” enzyme used by coronaviruses called SARS -CoV-2-PLpro.
According to the study published in the journal Science, SARS-CoV-2-PLpro promotes infection by detecting and processing viral and human proteins.
“This enzyme performs a double whammy,” according to the study, lead author Sean K. Olson is an associate professor of biochemistry and structural biology at UT Health San Antonio.
“It stimulates the release of proteins needed for the virus to replicate and 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, which help maintain protein integrity by acting like molecular scissors, he explained.
Scientists have developed inhibitors, which are very effective in blocking the activity of SARS-CoV-2-PLpro, but do not recognize other similar proteins in human cells.
“This is an important point: the inhibitor is specific to this single viral enzyme and does not cross react with human enzymes having a similar function,” he said.
The researchers said that this specificity would be a major determinant of the therapeutic value of the approach.
When scientists compared SARS-CoV-2-PLpro to similar enzymes from recent decades, such as the 2002–03 SARS pandemic virus, they found that it distinguished ubiquitin and ISG15 in ways very different from its counterpart.
“One of the main questions is whether we see how these viruses affect humans because of certain differences,” Olsen said.
By understanding the similarities and differences of these enzymes in different coronavir, the researchers said it would be possible to develop effective inhibitors against many viruses.
Olsen said these inhibitors could potentially be modified when other coronovirus variants emerge in the future.
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