To help stop the spread of COVID-19, a team of researchers is trying to stop a key enzyme that the virus needs to reproduce in human cells.
Biochemist, director of the Institute of Biomolecular Sciences of Miami Florida International University (FIU) Yuk-Ching Tse-Dinh and the deputy director of the center Prem Chapagain and the University of Texas Medical Branch (UTMB) and the National Cancer Institute The researchers collaborated. The team is looking for potential treatment clues, hoping that at least one of them can reduce the spread of the virus in infected people. There is currently no evidence-based treatment for COVID-19 or any other coronavirus.
Image source: Florida International University
Last month, Dr. Mariano Garcia-Blanco of UTMB reported his discovery on BioRxiv: Topoisomerase III-beta (TOP3B) is a host factor. Normally, topoisomerase helps DNA replication in human cells. However, when certain viruses, including dengue, Zika and SARS-CoV-2, attach to TOP3B, they use this enzyme to help assemble new copies of the virus and turn infected cells into virus factories.
After this discovery, Garcia-Blanco was helped by Tse-Dinh, an internationally renowned expert on topoisomerases, and began screening a drug that could block this enzyme and prevent COVID-19 from multiplying in the human body. Garcia-Blanco said: "We think FIU is the best source of inhibitors."
Tse-Dinh starts with drugs that the FDA has approved because she is looking for a treatment that can be quickly tested on patients. She said: "Our goal is a host factor, which is already present in human cells and hijacked by viruses. If the cells' TOP3B does not work, the virus will not be so effectively infected."
The researchers believe that antiviral drugs can be used in combination with TOP3B inhibitors, causing a double blow to the virus and improving the chances of recovery for critically ill patients.
Mike Heithaus, Dean of the FIU School of Arts, Science and Education, said: "Our researchers are focused on providing practical solutions to the biggest challenges facing our time. If this effort succeeds, it will be possible to exceed the current epidemic. It can provide a new method for treating other viruses and even emerging viruses. "
However, there are thousands of FDA approved drugs, and knowing where to start is a real challenge. This is the role of Chapagain. Chapagain said: "Many researchers have shifted their focus from their own projects to this project because COVID-19 suddenly hit us like a hammer."
Through artificial intelligence and molecular modeling, the physicist was able to quickly identify potential drug candidates as TOP3B inhibitors. Tse-Dinh and PhD students Ahmed Seddek and Tumpa Dasgupta have been testing these drugs with purified TOP3B and related topoisomerases. Garcia-Blanco's research team is currently testing live cell cultures and viruses including COVID-19.
Garcia-Blanco said: "This is a very simple story. We want to inhibit this enzyme. That's it. If we can do this and combine it with other antiviral treatments, it may increase to help critically ill patients. Opportunity."
Collaborators include Dr. Yves Pommier from the National Cancer Institute. They are highly focused and work in laboratories across the country for a long time, trying to stop TOP3B together. Garcia-Blanco even divided his research team into two smaller groups to maintain social distance and ensure that even if one of the groups had to be isolated, the work could continue. At the same time, Chapagain is working remotely in his home, perfecting his model, and continuing to look for other possible drug candidates.
"We did feel the urgency," Tse-Dinh said. "But we must be based on science."