Science Advances has published a study by the Institute of Clinical Physiology of the National Research Council of Pisa (CNR-IFC), under the coordination of Silvo Conticello, and by the Institute for the study, prevention and oncological network (ISPRO), together with researchers from the University of Florence, which shows how our cellular processes are able to “hack” the genetic code of Sars-Cov-2 through a process known as “RNA editing”.
he idea of this project stemmed from Giorgio Mattiuz, UNIFI research fellow, with colleagues Salvatore Di Giorgio and Filippo Martignano (Ispro) who carried out the bioinformatics analyses underpinning the publication.
ADARs and APOBECs, a group of enzymes with physiological roles that range from immunity to increasing cellular heterogeneity, are responsible for RNA editing. ADARs and APOBECs convert two of the four components of RNA - adenines and cytosines - into inosines and uracils, causing genetic alterations. The induced mutations on viral genomes do not always succeed in viral death and may indeed contribute to the viral evolution. The physiological factors that affect the editing efficiency may represent one of the variables involved in the individual response to the virus and their study may provide indications on host risk and prognostic factors.
“In the study the sequencing of the viral RNA, i.e. the technique used to assemble the sequence of viral genomes, was used for the first time by ISPRO colleagues Salvatore Di Giorgio and Filippo Martignano to identify low-frequency mutations, operated by the enzymes in the attempt to improve the defense mechanism,” explains Mattiuz.”
“Although RNA editing alone is not able to counteract the infection, having identified it highlights the presence of a virus's Achilles heel,” adds Conticello. “And the development of tools improving the process efficiency could be helpful to design therapies not only against Sars-Cov-2, but also against other viruses. In the short term, the analysis of the mutations inserted by ADARs and APOBECs can help us identify regions of the viral genome relevant for its life cycle: once identified, these information can help us develop targeted therapies to interfere with viral replication,” concludes the researcher.
