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Popular Science: One more piece to the coronavirus puzzle?

Dozens of millions of infected people all over the world, nearly two and a half million deaths, and normal life on hold… all because one virus, which obviously is the new coronavirus SARS-CoV-2 causing the disease known as covid-19. In addition to the development of vaccines and drugs, the characterisation of individual parts of the virus particles is another very important part of research. This part of research was of interest to the team led by Václav Veverka and Evžen Bouřa from the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB CAS) and the Faculty of Sciences of Charles University. They published an article with the main authors being Dhurvas Chandrasekaran Dinesh and Dominika Chalupská from IOCB CAS.

Given the ongoing pandemic, it is not surprising that the coronavirus attracts the attention of scientists all over the world. The characterisation of its individual particles is crucial for understanding the virus behaviour and the possible development of new vaccines and drugs.

Coronaviruses belong to the group of RNA viruses, which means that their genetic information is coded by ribonucleic acid. Like other known coronaviruses, SARS-CoV-2 has unusually large genetic information for an RNA virus. It codes 20 proteins in total with 16 of those being non-structural proteins (they play a role in the life cycle of the virus) and 4 being structural proteins. The latter form a membrane, a small envelope – the spike protein that is responsible for the recognition of and entry into cells, and nucleocapsid phosphoprotein which physically links the genetic material to the envelope and is essential for packing the new virus particles emerging from the cell.

Backbone of the binding site of nucleocapsid protein,
source: original article.

It was the last protein mentioned that was the target of this study. Scientists managed to obtain its structural model in high resolution using nuclear magnetic resonance (the NMR method capable of determining the structure of molecules). The model included the way in which this protein links the genetic material to the virus envelope. It turns out that the protein only binds the backbone of the RNA, which explains the unspecific nature of the bond between the protein and the genetic material because the backbone is independent of the specific information coded in the RNA.

All parts of the research have one common goal, which is to return the whole society back to normal life. The biggest hope for going back currently is vaccination and the development of new drugs. For quite a while, the most promising drug was remdesivir, which was originally developed for treating ebola by a team lead by Czech scientist Tomáš Cihlář. It targets one of the non-structural proteins responsible for the production of new genetic material while the virus reproduces in the cell. However, the World Health Organization did not recommend the use of remdesivir in November 2020. So, the efforts to develop new drugs continue. The most effective treatment can consist of a combination of active substances targeting various parts of the virus. This approach has proven effective in treating AIDS and other diseases. The newly characterised nucleocapsid protein can thus be another potential target for newly synthesized drugs against the coronavirus. The only downside is that it can be very difficult to target a structural protein with such a large binding site.

Dinesh DC, Chalupska D, Silhan J, Koutna E, Nencka R, Veverka V, et al. (2020) Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein. PLoS Pathog 16(12): e1009100.

Magda Křelinová

Published: Mar 15, 2021 04:10 PM

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