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INRA
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Dernière mise à jour : Mai 2018

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Will RNA therapy be able to beat SARS-CoV-2 during a respiratory infection?

24 April 2020

@INRAE E. Barrey
Two INRAE (Jouy-en-Josas) teams and a laboratory in Santiago, Chile put their expertise in virology and molecular biology of RNA together to conceive, via bioinformatics, a series of antisens oligonucleotides that, by specifically binding to key viral genome regions of SARS-CoV-2, could destroy and therefore block viral multiplication.

The COVID-19 pandemic has provoked a world sanitary and economic crisis and today, no specific treatment exists. Future vaccines will be the good solution to fight the virus on the world population scale but at an individual scale, the virus, which is well-adapted to man, will continue to circulate and make many people sick who will need efficient and specific treatments.

The coronavirus SARS-CoV-2  possesses an RNA genome, that is both its strength but also its weakness, which may be specifically cut using moleuclar tools called antisens oligonucleotides that have been chemically modified. With these molecular tools, we will target key regions that allow the virus to replicate its viral genome and transcribe viral genes into proteins.

By using RNA therapy technologies that are currently being developed clinically for different diseases such as cancers, certain myopathies or degenerative diseases of the nervous system (such as Huntinton Disease) but also against the virus, we conceived a series of antisens oligonucleotides using bioinformatics tools. These oligonucleotide molecules are chemically modified in order to remain stable over time and bind to their targets, by irreversible complementary hybridation, to the vital regions of the viral genome. Once binded, the antisens oligonucleotides form a viral DNA-RNA double strand that will systematically be cut by natural enzymes (RNAse H1) of the infected cells. These irreversible cleavages of the viral genome and/or its transcripts wil block its replication and by consequence its multiplication. Our bioinformatics study shows that RNA therapy using two different technologies could theoretically be used to reduce viral infection of cells infected by SARS-CoV-2. A previous experimental study by an analogous method on the first SARS-CoV has already shown the feasibility of this type of treatment which is encouraging for the future of the project.

What are the perspectives after these preliminary results obtained by bioinformatic caluclations? Now an experimental demonstration in a virology laboratory of the efficiency of these treatments by antisens oligonucleotides on cell models infected by SARS-CoV-2 must be performed. Although some candidates seem efficient alone or combined, to significantly decrease viral multiplication, a preclinical trial on an in vivo model will be necessary before a real clinical trial on man can be done. If we refer to RNA therapy clinical trials that have already been done or are currently underway, the enormous advantage of these antisens oligonucleotide technologies is their specificity, good tolerance, low toxicity and reasonable cost of production of these molecules. Finally, for COVID-19 which mainly affects the lungs, the administration by inhalation using a nebulizer of an aqueous solution containing antisens oligonucleotides will allow to directly reach the virus in the respiratory pathways at an early stage of the disease. In addition, these small antisens oligonucleotides are naturally absorbed by cells and do not need a vector nor solvant to reach their therapeutic targets.

A long way remains still but it is possible with partnership. This is the reason why a paper is available on line before editing and publication in an international scientific journal, in order to share the results of this prediction with the scientific community and stimulate partnerships and laboratory tests wherever that is possible in good, secure and efficient conditions. At INRAE of Jouy-en-Josas, the units Molecular Virology and Immunology (UMR VIM) and  Animal Genetics and Integrative Biology (UMR GABI) are preparing 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?

https://www.preprints.org/manuscript/202004.0412/v1

Eric Barrey 1 , Veronica Burzio 2, Sophie Dhorne-Pollet 1,   Jean-François Eléouët 3, Bernard Delmas 3

 

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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