A SARS-CoV-2 replicon: a useful system for studying the virus

In order to fight SARS-CoV-2 and equip ourselves with effective therapies, we need to study and test candidate treatments. It is, however, complicated to use the virus in cell culture, mainly for safety reasons. This is a contagious and dangerous virus and it is best to avoid handling it. Researchers at the Universities of Rockefeller (New York, USA) and Berne (Switzerland) have developed a molecular biology tool that enables a SARS-CoV-2 virus to be produced that reproduces in cells in vitro (cell culture) but which is not infectious.

The researchers developed what we call a replicon for SARS-CoV-2, a molecule of RNA or DNA that is self-replicative. This is a tool that was developed for other viruses, such as hepatitis C. Replicons enable a part of the cycle of the virus to be studied without producing infectious particles. The principle is to suppress a part of the viral genome to prevent it producing one of its proteins. Since it lacks a key component, the virus will not be infectious.

In this way, the scientists constructed a replicon made up of the RNA of SARS-CoV-2, that is, its genome, having suppressed the gene that encodes the protein of the spike, a protein that is indispensable for the virus to be able to enter the cell. The replicon is therefore introduced into cell cultures and the cell’s machinery is used to produce different SARS-CoV-2 proteins encoded by the replicon. In those cells that express this replicon in a stable way, it becomes possible to temporarily insert the RNA of the spike protein. This allows the entry of viral particles carrying the spike protein of different variants to be studied without an infectious virus being present.