These 4 things could block COVID-19, study shows

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A recent study at the University of South Florida Health and elsewhere found 4 existing compounds that block replication of the COVID-19 virus (SARS-CoV-2) within human cells grown in the laboratory.

The most promising drug candidates, including the FDA-approved hepatitis C drug boceprevir and an investigational veterinary antiviral drug known as GC-376, target the SARS-CoV-2 main protease (Mpro), an enzyme that cuts out proteins from a long strand that the virus produces when it invades a human cell.

Without Mpro, the virus cannot replicate and infect new cells.

The study is published in Cell Research. One author is Yu Chen, PhD, USF Health associate professor of molecular medicine.

As the death toll from the COVID-19 pandemic mounts, scientists worldwide continue their push to develop effective treatments and a vaccine for the highly contagious respiratory virus.

The enzyme Mpro had already been validated as an antiviral drug target for the original SARS and MERS, both genetically similar to SARS-CoV-2.

A lot of good drug candidates are already out there as a starting point.

But, with new information from studies like this and current technology, researchers can help design even better (repurposed) drugs much faster.

The four leading drug candidates identified as the best (most potent and specific) for fighting COVID-19 are described below.

These inhibitors rose to the top after screening more than 50 existing protease compounds for potential repurposing:

Boceprevir, a drug to treat Hepatitis C, is the only one of the four compounds already approved by the FDA.

Its effective dose, safety profile, formulation, and how the body processes the drug (pharmacokinetics) are already known, which would greatly speed up the steps needed to get boceprevir to clinical trials for COVID-19.

GC-376, a veterinary drug for a deadly strain of coronavirus in cats, which causes feline infectious peritonitis.

This drug was the most potent inhibitor of the Mpro enzyme in biochemical tests, but before human trials could begin it would need to be tested in animal models of SARS-CoV-2.

Calpain inhibitors II and XII, cysteine inhibitors tested in the past for cancer, neurodegenerative diseases and other conditions, also showed strong antiviral activity.

Their ability to dually inhibit both Mpro and calpain/cathepsin protease suggests these compounds may include the added benefit of suppressing drug resistance.

All four compounds were superior to other Mpro inhibitors previously identified as suitable to clinically evaluate for treating COVID-19.

Instead of promoting the activity of the viral enzyme, like the substrate normally does, the inhibitor strongly decreases the activity of the enzyme that helps SARS-CoV-2 make copies of itself.

The team says visualizing 3-D interactions between the antiviral compounds and the viral protein provides a clearer understanding of how the Mpro complex works and, in the long-term, can lead to the design of new COVID-19 drugs.

In the meantime, they focus on getting targeted antiviral treatments to the frontlines more quickly by tweaking existing coronavirus drug candidates to improve their stability and performance.

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