Next COVID-19 Drug Enemy – The Viral “Molecular Scissor”

The novel coronavirus uses an enzymatic cutter for virus production that also disables essential immune proteins.

The Plan

American and Polish scientists, reporting October 16, 2020, in the journal Science Advances, put together a new plan for a potential drug against the lethal virus – blocking the so-called “molecular scissor” the virus uses for replication and disabling crucial proteins.

The team consists of researchers from The University of Texas Health Science Center from San Antonio (UT Health San Antonio) and the Wroclaw University of Science and Technology.

The information gathered by the American scientists helped Polish chemists produce two molecules that inhibit the virus’ cutter, an enzyme that got the name SARS-CoV-2-PLpro.

The newly-created enzyme promotes infection by detecting and processing both human and viral proteins, according to senior author Shaun K. Olsen, Ph.D., an associate professor of biochemistry and structural biology in the Joe R. and Teresa Lozano Long School of Medicine from UT Health San Antonio.

Dr. Olsen stated:

“This enzyme executes a double-whammy [… ] It stimulates the release of proteins that are essential for the virus to replicate, and it also inhibits molecules called cytokines and chemokines that signal the immune system to attack the infection.”

The inhibitor is specific for a single viral enzyme and does not cross-react with other human enzymes that work similarly, Dr. Olsen said.

The American team compared SARS-CoV-2-PLpro against related enzymes from past coronaviruses, like MERS and SARS-CoV-1. They found out that SARS-CoV-2-PLpro processes ISG15 and ubiquitin in a different way than its SARS-1 predecessor.

Dr. Olsen and his team are trying to determine the differences between the two could mean and how they can use them against the recent virus.

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