American and Swiss researchers have created coronavirus replicons – self-replicating RNAs that are identical to the virus, but non-infectious. Article by scientists published in Science magazine.
In order to study the effect of such a contagious virus as SARS-CoV-2, experts are forced to do it in compliance with strict protocols in biosafety laboratories. They can be made easier by replicons that replicate nearly every aspect of the virus’s life cycle. They are usually created by cloning the RNA genome into DNA fragments in test tubes, from which synthetic RNAs are then obtained. But the RNA of the coronavirus is extremely long.
Therefore, researchers from the Universities of Berne and Rockefeller University, led by the 2020 Nobel laureate in physiology or medicine Charles Rice, took a different approach: fragments of the coronavirus genome were “assembled” in small fragments, but not in test tubes, but in baker’s yeast. The resulting genome contains all the information needed to replicate the virus – except for the “instructions” for assembling the S-protein, which allows the virus to penetrate and infect cells.
However, this protein is the main focus of a large number of coronavirus research. To get around this obstacle, the researchers expressed the S-protein in parallel with the replicon. The resulting particles are able to penetrate cells, but in their infectivity are limited to one cycle of the life of the virus.
Virologists hope that their replicons will help scientists figure out many previously unknown details of how the coronavirus works, as well as test the effectiveness of drugs against COVID-19. So, in one of the experiments, scientists tested the effect of remdesivir on a replicon. “We found that it suppresses replicon at the same concentrations as the actual virus. This shows that the replicon system can be a reliable alternative to SARS-CoV-2 in the testing of various drugs, ”noted the first author of the work, Inna Ricardo Lax.
