RA-COVID-19 V10 - Recherche - Action Coronavirus disease 2019 - Vague 10

Identification of SARS-Cov-2 neutralizing Affitins – COVAFFIT

Submission summary

The emergence in 2019 of a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) has led to a global pandemic with nearly 31 million infected people of whom nearly 1 million have died. This virus is particularly contagious and uses the S protein (or spike protein) through its RBD domain to recognize and infect cells via an interaction with the angiotensin-2 converting enzyme (ACE2). Their interaction leads to fusion of the membranes of the virus and the host cell. The S protein is known to induce neutralizing antibodies and many research efforts focus on the development of this kind of molecules as therapeutics. To maximize our chances to fight efficiently the virus it is important to expand as most as possible the panel of potential therapeutics available by using affinity proteins structurally unrelated to antibodies in order to target different epitopes and that could possibly have different or complementary biological effects.
The aim of the COVAFFIT project is to generate, identify and characterize small artificial affinity proteins (Affitins) able to prevent viral entrance into cells. Affitins are tailor-made, 20 times smaller than antibodies, robust, non-immunogenic, cheap to produce, affinity and patented proteins that we have developed from an extremophile protein. We have also shown that Affitins can inhibit biological processes and thus represent an appealing substitute or complement to antibodies.
To this aim we will generate in vitro Affitins from synthetic 10^12 variants libraries using RBD domain, S protein and pseudotyped particles as targets. Using a high throughput in vitro test we have developed to identify neutralization molecules, we will screen and identify Affitins able to neutralize SARS-Cov-2 infection. The best Affitins candidates will be then characterized in vitro for their affinity, specificity and ability to prevent viral entrance into cells. We believe these identified Affitins will provide novel antiviral molecules able to neutralize SARS-Cov-2.

Project coordination

Frédéric Pecorari (Inserm U1232)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

P2R P2R Proteines recombinantes-Inserm U1232
CRCINA Inserm U1232
IP - Virus & Immunity unit INSTITUT PASTEUR- Virus and Immunity unit

Help of the ANR 147,960 euros
Beginning and duration of the scientific project: February 2021 - 12 Months

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