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By using RNA therapy techniques currently being developed clinically for many diseases like cancers, certain myopathies or degenerative diseases of the nervous system (such as for Huntington disease) but also against viruses, we have conceived a series of antisense oligonucleotides using bioinformatics tools. These oligonucleotides are chemically modified in order to remain stable over time, so that they will fix onto their targets, by irreversible complimentary hybridation, located in vital regions of the viral genome. Once collected, these antisense oligonucleotides  form a double strand viral DNA-RNA that will be systematically cleaved by two natural enzymes (RNAse H1) of the infected cells. These irreversible cleavages of the viral genome and/or their transcripts will block the virus' replication and as a consequence its multiplication. Our bioinformatics study therefore showed that RNA therapy using two different techniques would be theoretically usable to decrease viral infection of the cells infected by SARS-CoV-2. A previous experimental study by a similar method on SARS-CoV showed that this type of treatment is doable, which is encouraging for the rest of the project.

What are the perspectives after these preliminary results obtained through bioinformatics calculations? Now, we must demonstrate experimentally in a virology laboratory the efficiency of these treatments using antisense oligonucleotides on of SARS-CoV-2 infected cell models. If some of our candidates are shown to be efficient alone or combined, significantly decreasing viral multiplication, a preclinical assay on an in vivo model will be necessary before a real clinical trial in man may begin. Considering previous clinical trials of RNA assays of those currently underway, the great advantage of antisense oligonucleotides is their high specificity, good tolerance, low toxicity and reasonable production costs of these molecules. Finally, for COVID-19 which mainly affects the lungs, the administration by inhalation of an aqueous solution containing the antisense oligonucleotides will allow to reach directly the virus located in the respiratory tract at an early stage of the disease. In addition, these small antisense oligonucleotides are naturally absorbed by the cells and do not require a vector nor special solvent to reach their therapeutic targets.

There is still a long way to go but it is feasible with collaborative work. This is the reason why this paper is available on line before revision and publication in an international scientific journal, in order to share the results of these predictions with the scientific community and to stimulate partnerships and laboratory tests wherever this is feasible while respecting high standards of security and efficiency. At INRAE Jouy-en-Josas, the Molecular Virology and Immunology unit (UMR VIM) and Animal Genetics and Integrative Biology Unit (UMR GABI) are preparing their teams to this experimental approach.