The two Sicilian researchers aiming for the coronavirus “Achilles heel”

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CATANIA – Today’s number one public enemy, Sars-CoV-2, has its Achilles’ heel. The discovery comes from a group of researchers coordinated by a Catania, Silvio Conticello, from the Institute of Clinical Physiology of the National Research Council of Pisa (Cnr-IFC) and the Institute for the study, prevention and cancer network (Ispro ) and starring another Sicilian, Salvatore Di Giorgio (researcher from Palermo), and Giorgio Mattiuz from the University of Florence.

Human cells “hack” the Sars-CoV-2 virus to activate one of the immunity mechanisms. And they do it thanks to the editing of RNA (ribonucleic acid). This is the discovery, published in “Science Advances”.

In the work, the RNA sequencing of the virus, that is, the technique used to calculate the sequence of viral genomes, was used for the first time to identify low-frequency mutations operated by enzymes to attempt to implement the defense mechanism.

“I have been working for years to understand the meaning of RNA editing – explains Salvatore Di Giorgio -, I had put on a pipeline, that is computational processes / procedures, through which I analyzed samples from tissues and cells, healthy or affected by pathologies. It was natural, as soon as the virus data was available, to analyze it. The involvement of RNA editing was already known – continues the Palermitan researcher – in an antiviral key, but no one had identified the mutations induced by Adar and Apobec directly on the viruses obtained by the patients, modifying a technique used for the assembly of the viral sequences “.

– What is the strong point of this study?

“Even if the editing of the RNA alone is not able to counteract the infection – underlines the researcher from Catania Silvio Conticello -, having identified it highlights a weak point, an Achilles heel. Developing tools to improve this process could pave the way for therapies. Furthermore, the analysis of the mutations inserted by the Adar and Apobec, a group of enzymes with physiological roles that range from the processes of immunity to the increase in heterogeneity within the cells, which substantially modify two of the components of the RNA – the adenines to the cytosines in inosines and uracils – in order to alter the genetic code of the virus, it can help to identify regions of the viral genome important for its life cycle: this information can help, therefore, to develop targeted therapies to block the replication of the virus directly inside the cell “.

The effects of these mutations, however, they are not always effective in fighting infection. «Unfortunately – explains the Etna scholar – induced mutations do not always succeed in damaging the viral genome and can actually contribute to the evolution of the virus. The physiological factors that influence the effectiveness of editing can however represent one of the variables that determine the individual response to the virus and their study could provide indications on risk and prognostic factors “.



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