Virus Inhibition by siRNA Optimized by NMR

Project Information

VISION

Grant agreement ID: 101081838

DOI

10.3030/101081838

Project closed

EC signature date 16 August 2022

Start date 1 September 2022

End date 29 February 2024

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - VISION (Virus Inhibition by siRNA Optimized by NMR)

Reporting period: 2022-09-01 to 2024-02-29

Summary of the context and overall objectives of the project

On the contrary of bacterial infections that we can fight with antibiotics, we do not possess similar molecules to acts against viruses. Conceiving such molecules remains a major challenge. This was recently illustrated with the COVID-19 pandemics: despite two thousands clinical trials of divers nature, very few molecules have made it to the clinic and their efficacy still needs to be proven on severe cases. Currently, most of the treatments consist in attenuating the symptoms of the disease. Being able to obtain antivirals that can treat such infections is therefore of major interest for public health and would be a major tool to complement current treatments and vaccines.
siRNAs (small interfering RNAs) are synthetic mimics of microRNAs, some short non-coding RNA regulating the genetic expression using the RNA interference mechanism. With this mechanism the miRNA can interact with a messenger RNA (mRNA) coding for a protein and block its translation. The core of the VISION project is to design and optimize such siRNA to obtain an efficient anti-SARS-CoV-2 molecules.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the course of the project, we have designed a series of siRNA and demonstrated their efficacy in vitro against SARS-CoV-2. We have optimized their chemical structure to make them much more stable. In fact, in the organism the degradation of siRNA can be very fast but by adequate changes in their chemical composition, we have efficiently boosted their stability. By using NMR spectroscopy, a tool to look at molecular interaction at the atomic scale, we have characterized the interaction of our siRNA with its targets. We are also currently finalizing some tests of the siRNA in reconstituted epithelium, a step that will allow to move closer to physiological environments.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Here, we demonstrated that siRNA can be designed and optimized to be potential therapeutics again viruses. Although this a great success, the route towards a molecule used in clinics is long and complex. To achieve this long-term goal, numerous work directions still need to be investigated: additional research is necessary to further understand how those molecules work, testing the molecule efficacy and toxicity in vivo or later in patients will be needed, IPR support will be necessary to ensure a proper development of these molecules and an up-scaling towards clinical trial and commercialization will be in fine needed to ultimately obtain an antiviral.