Warsaw researchers develop new selection method of potential SARS-CoV-2 antiviral agents
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Researchers from the University of Warsaw have developed a new method of selection of compounds that counteract the formation of SARS-CoV-2 viral proteins. They examined 7,000 compounds and selected 83 that inhibit the function of the viral enzyme.
Both pharmaceutical companies and academic teams are currently looking for substances that will be able to effectively disrupt the expression of the SARS-CoV-2 genetic material, and thus become the basis for developing a drug against COVID-19.
Research in this area is also conducted by a team from the University of Warsaw, headed by Professor Jacek Jemieliety and Dr. Joanna Kowalska. The researchers analyse the possibility of using nsp14 methyltransferase inhibitors, a SARS-CoV-2 virus enzyme. The activity of this enzyme is responsible for the replication of the SARS-CoV-2 virus. It is necessary for the viral RNA to be efficiently translated in human cells, resulting in viral proteins leading to viral replication. The university informs about the research on its website.
The researchers have developed a fluorescence-based assay for the high-throughput screening (HTS) of potential N7-methyltransferase inhibitors. With this method, out of 7,000 compounds they selected 83 structures that inhibited the viral enzyme.
The researchers also checked how these compounds acted on the human equivalent of this enzyme, and on this basis they chose 33 compounds showing greater reactivity in relation to the viral enzyme for further research.
In collaboration with the Laboratory of Virology and Chemotherapy at the Rega Institute for Medical Research, researchers checked the effectiveness of selected compounds in combating the virus in cellular models infected with SARS-CoV-2. Three of the selected compounds showed effectiveness in these tests. The best of them was pyrodostatin, which effectively destroyed the virus in cells while not showing toxic effects for healthy cells.
In the future, the results of research carried out by scientists from the University of Warsaw can lead to the development of effective drugs against COVID-19. Results of the team's work are not protected by a patent. Companies interested in further development of antiviral drugs based on the selected compounds may continue research without the need to purchase a license.
Professor Jacek Jemielity from the Centre of New Technologies of the University of Warsaw, said: “SARS-CoV-2 vaccines are a huge step towards ending the pandemic caused by the SARS-CoV-2 virus. But years may pass before that happens, especially if we do not accelerate the rate of vaccination. There are still no effective methods of treating people who have already become ill with COVID-19. Our discovery is important, but only the first step on an expensive and long road to effective antiviral therapy.”
The research results have been published in the scientific journal Antiviral Research (https://www.sciencedirect.com/science/article/pii/S0166354221001327) (PAP)
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