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INRA
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Dernière mise à jour : Mai 2018

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Could RNA therapy fight SARS-CoV-2 during a respiratory infection?

27 April 2020

@INRAE E. Barrey
Two INRAE teams (Jouy-en-Josas) and a laboratory in Santiago du Chili have used their expertise in bioinformatics and virology and molecular biology of RNA antisens oligonucleotides that, when specifically binding themselves to key regions of the SARS-CoV-2 viral genome, will destroy them and block viral multiplication.

The COVID-19 pandemic has provoked a world health and economic crisis, and as to date, no specific treatment exists. Future vaccines will be the good solution to fight the virus on the world level but on the individual level, the virus which is well-adapted to man, will continue to circulate, infect and sicken many people who will need to be treated with efficient and more specific treatments.

SARS-CoV-2 coronavirus possesses an RNA genome, which is both its strength and its weakness; using molecular tools called antisens oligonucleotides that have been chemically modified, it is possible to block the virus. With these molecular arms, key regions of the virus that allow the viral genome to replicate and transcribe viral genes into proteins will be targeted.

Using RNA therapy technology, which is currently under clinical development for several diseases like cancer, certain myopathies or degenerative diseases of the nervous system (such as Huntington's disease) but also against viruses, we have conceived a series of antisens oligonucleotides using bioinformatics tools. These oligonucleotide molecules are chemically modified in order to remain stable over time and to bind to their targets, by irreversible complementary hybridation, to the vital regions of the viral genome.

Once bound, these antisens oligonucleotides form a viral DNA-RNA double strand that will be systematically cut by natural enzymes (RNAse H1) from the infected cells. These irreversible cleavages of the viral genome and/or its transcripts will block its replication and as a consequence, its multiplication. Our bioinformatics study shows that RNA therapy using two different technologies would theoretically be usable to reduce viral infection of cells infected by SARS-CoV-2. A previous experimental study using an analogous method on the first SARS-CoV virus had already shown the feasibility of this type of treatment which is encouraging for the future of this project.

What are the perspectives after these preliminary results obtained through bioinformatics calculations? An experimental demonstration in a virology laboratory of the efficiency of these treatments with antisens oligonucleotides on model cells infected by SARS-CoV-2 are now necessary. Although some of our candidates seem efficient, alone or combined, to significally decrease viral multiplication, a pre-clinical trial on an in vivo model would be necessary before a real clinical assay on man may be begun. If we refer to clinical trials for RNA therapy currently used or underway, the greatest advantage of these antisens oligonucleotide technologies is their high specificity, good tolerance, low toxicity and reasonable production cost of these molecules. Finally, for COVID-19 that mainly affects the lungs, the administration through inhalation of an aqueous solution containing antisens oligonucleotides as a spray would enable directly reaching the virus through the respiratory pathways at an early stage of the disease. In addition, these small antisens oligonucleotides are naturally absorbed by the cells and do not need a vector nor a special solvant to reach their therapeutic targets.

The road is still long but it is feasible with collaborative work; this is the reason for which an article is available on-line before revision and publication in an international scientific journal, in order to share these prediction results with the scientific community and stimulate partnerships and laboratory tests everywhere where these experiment may be performed under good, safe and efficient conditions. At INRAE in Jouy-en-Josas, the Molecular Virology and Immunology Laboratory (UMR VIM) and the Animal Genetics and Integrative Biology Laboratory (UMR GABI) are preparing for this experimental approach.  

See also

Reference:    
Think Different with RNA Therapy: Can Antisense Oligonucleotides Be Used to Inhibit Replication and Transcription of SARS-Cov-2?

 

Affiliations:

  1. Université Paris-Saclay, INRAE,  AgroParisTech,  GABI, 78350 Jouy-en-Josas, France.
  2. Department of Biological Sciences, Faculty of Life Sciences, Universidad Andrés Bello - Fundación Ciencia & Vida, Andes Biotechnologies SpA, Santiago, Chile
  3. Université Paris-Saclay, INRAE,  AgroParisTech,  UMR VIM, Virologie et Immunologie Moléculaire, 78350 Jouy-en-Josas, France.

 

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