Another success of scientists from the Wrocław University of Technology – winners of the FNP programmes. Their research results on one of the SARS-CoV-2 enzymes’ structures have just been published in the Science Advances journal. The primary author of the research paper is Wioletta Rut Ph.D., winner of the START programme. The research was conducted in the laboratory of prof. Marcin Drąg, a multiple winner of the FNP programmes and the 2019 FNP Prize. The research was conducted under the TEAM programme of the Foundation for Polish Science.
Researchers from Wrocław – together with scientists from the USA – decoded one of the SARS-CoV-2 enzymes’ structures and found a substance that completely inhibits its action. It represents a promising target for developing antiviral drugs that will stop the virus responsible for COVID-19 from replicating inside human living cells. The last few days have clearly shown that the pandemic is not letting go and is definitely gaining momentum. Pharmaceutical companies are working intensively on the next phases of vaccine testing, hoping that they will help stop the coronavirus spread. Antiviral drugs can be an alternative to vaccination.
“It has been known for years that vaccines against coronaviruses are difficult to create. The research on other solutions to these pathogens has not been popular because coronaviruses have not been a significant problem. In 2003, only about 8,000 people suffered from SARS, less than 800 died, “ says prof. Marcin Drąg from the Department of Biological Chemistry and Bioimaging, Wrocław University of Technology.
The Polish scientist had the opportunity to deal with the previous coronavirus. He conducted research on the structure of the SARS-causing pathogen. Due to the close phylogenetic relationship between SARS-CoV and SARS-CoV-2, he undertook to determine to what extent their main enzymes (proteases) share many structural and functional features.“We have conducted comparative research as the only research group in the world dealing with the issue. It turned out that the papain-like protease (PLpro) is identical in both cases, “ stated Prof. Drąg.
Where does this enzyme come from? When a virus enters a cell, it replicates and produces structural proteins. Then, proteases are released (SARS-CoV-2 has two of them, including PLpro), which “cut” and break the proteins down into smaller components. In this way more proteins are created that enable the virus to replicate.
PLpro also has another function in the infected cell. It processes human proteins, making it difficult for the immune system to fight the infection. In this way, the virus replicates in the cell without any hindrance, encoding its own replication until it is destroyed. And it spreads further from cell to cell. So, as you can see, receiving a substance that neutralizes the activity of the PLpro enzyme could completely stop the spread of the virus in the body and thus cure COVID-19.
This is what the team of prof. Drąg in cooperation with groups of prof. Tony Huang (New York University School of Medicine) and Shaun Olsen (Medical University of South Carolina) have achieved. “We sent inhibitors, i.e., substances that inhibit the activity of PLpro, to the United States in the hope of obtaining their crystal structure, which succeeded. Crystalline structures play an essential role in drug development. We tested many compounds, various drug derivatives, we managed to identify molecules that bind very well with this protease,“ says Prof. Drąg.
Since there is a considerable similarity between the enzymes of SARS-CoV and SARS-CoV-2, the creation of one drug gives hope for the effective treatment of the entire group of pathogens. “If we manage to develop a drug, it is highly probable that it will also work for the next coronavirus of the same type. It is a greater chance compared to the vaccines because they are based on completely different proteins. Proteins targetted by vaccines easily mutate, whereas proteases do not,” emphasizes prof. Drąg.
The scientists from Wrocław published the article on 16 October 2020 in the prestigious Science Advances journal. From April, it was available online as the so-called preprint on bioRxiv, but now it is coming out in full version with a few additional studies.
The Foundation for Polish Science implements the TEAM programme with EU funds from the European Regional Development Fund under the Smart Growth Operational Programme, axis IV: Increasing the scientific and research potential, 4.4 Increasing the human potential in the R&D sector.
In the photos: Wioletta Rut, Ph.D. / photo: private archive, prof. Marcin Drąg / photo. Bartek Sadowski