Covid-19: a study shows the success of enzyme inhibitors in the treatment

A study published this Friday (26) by Penn State University in the United States has identified a series of drugs approved by the Food and Drug Administration (FDA), the country’s regulatory body, which reduce “significantly “the ability of the Delta variant of covid-19 to replicate in human cells. The results were published on February 25 in the journal Communications Biology.

According to the Penn State researchers, the discovery encompasses drugs that inhibit viral enzymes essential for SARS-CoV-2 replication in infected human cells.

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“Vaccines against SARS-CoV-2 target the spike protein, but this protein is under strong selection pressure and, as we have seen with Ômicron, can mutate significantly”, explained the professor of Penn State Biochemistry and Molecular Biology, Joyce Jose.

In this regard, he added, “there remains an urgent need for therapeutic agents that target parts of the virus in addition to the protein. peakwhich is less likely to evolve”.

Previous research has shown that two SARS-CoV-2 enzymes – proteases, including Mpro and PLpro – are promising targets for antiviral drug development.

Penn State biochemistry and molecular biology professor Katsuhiko Murakami said the novel coronavirus makes long proteins, called polyproteins, from its RNA genome.

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“These proteins must be cleaved into individual proteins by these proteases in an orderly fashion, leading to the formation of functional viral enzymes and proteins to initiate virus replication as soon as it enters the cell. If you inhibit one of these proteases, the spread of the virus in the infected person can be stopped,” he explained.

Compounds tested

The researchers conducted trials that tested 64 compounds – including HIV and hepatitis C protease inhibitors; cysteine ​​proteases, present in some protozoan parasites; and dipeptidyl peptidase, a human enzyme implicated in type 2 diabetes (for its ability to inhibit Mpro or PLpro).

“Of the 64 compounds, the team identified 11 that affected Mpro activity and five that affected PLpro activity, based on a threshold of 50% protease activity with cell viability by 90%,” the university said.

Next, the team assessed the antiviral activity of the 16 PLpro and Mpro inhibitors against viruses in live human cells, and found that eight of them had “dose-dependent antiviral activities against SARS-CoV-2 , and that some of them inhibit the Mpro enzyme.” , in addition to altering the ability of the virus to infect cells.

The researchers also found that the combination of certain substances provided an “additive antiviral effect”, further inhibiting the replication of the novel coronavirus.

While the scientists studied the Delta variant, they say the drugs “are likely to be effective against Omicron and future variants because they target parts of the virus that are not likely to mutate significantly.”

*With information from Penn State University.

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