Blocking Key Enzyme in Human Cell Could Prevent COVID-19 from Multiplying

The researchers are searching for potential treatment leads in the hope that at least one of them will reduce the spread of the virus in infected individuals.

In March this year, UTMB researchers had discovered that coronaviruses rely on the enzyme Topoisomerase III-ß (TOP3B) as a host factor. Normally, topoisomerases aid in DNA replication within human cells. But when certain viruses, including Dengue, Zika and COVID-19, latch on to TOP3B, they use the enzyme to help assemble new copies of the virus, turning infected cells into virus factories. The team of researchers is now making a joint effort to start screening for a drug that could block the enzyme and prevent COVID-19 from multiplying in high numbers in a person’s body. The researchers have started with drugs already approved by the Food and Drug Administration as the aim is to find a treatment that can be tested quickly on patients. The researchers believe antiviral medications could be administered in tandem with a TOP3B inhibitor to deliver a double blow to the virus and improve chances of recovery for those who are critically ill.

However, with thousands of FDA-approved drugs, knowing where to begin is a real challenge. Using artificial intelligence and molecular modeling, the researchers have been able to quickly identify top drug candidates that could possibly serve as TOP3B inhibitors. After testing those drugs against a purified version of TOP3B and related topoisomerases, the researchers are now testing them against live cell cultures and viruses, including COVID-19.

“It’s a very simple story,” said Dr. Mariano Garcia-Blanco from UTMB. “We want to inhibit this enzyme. That’s it. If we can do that and combine it with other anti-viral treatment, it could enhance the chances to help people who are very ill.”

“Our researchers are focused on real, tangible solutions for the greatest challenges of our time,” said Mike Heithaus, dean of FIU’s College of Arts, Sciences & Education. “This effort, if successful, has potential beyond the current pandemic. It could provide a new approach to treating other viruses and even emerging ones.”

Related Links:
FIU Biomolecular Sciences Institute
University of Texas Medical Branch
National Cancer Institute