RA-COVID-19 V7 - Recherche - Action Coronavirus disease 2019 - Vague 7

Inhibition of SARS-Cov2-S - ACE2 interaction AS A THERAPEUTIC TARGET – ACE2-S-Cov

Submission summary

Coronavirus disease 2019 (COVID-19), which is caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become pandemic, in the absence of an approved drug treatment or prophylactic vaccine. The virus surface spike protein (S), which mediates coronavirus entry into the cell, is an attractive target for the development of antiviral molecules. The S protein contains a receptor-binding domain (RBD) that specifically interacts with angiotensin-converting enzyme 2 (ACE2). ACE2 is an essential component of the renin–angiotensin system (RAS) that is expressed in lung alveolar epithelial type II cells. Several studies have reported resolutions of the structure of SARS-CoV-2–S complexed with human ACE2. The residues involved in the formation of this complex were mapped to positions 481-493 of the viral protein and a stretch of almost 20 residues of ACE2. Knowledge of the spatial organization of this large binding interface is useful for the design of small molecules counteracting the formation of this complex. The aim of this project is to evaluate the effect of a series of patented molecules targeting the SARS-CoV-2 -S protein / ACE2 interaction. It brings together researchers with complementary expertise in drug design (structural bioinformatics and chemoinformatics), medicinal chemistry and virology, to identify compounds with potent antiviral effects.

Project coordinator

Monsieur Hugues de rocquigny (Morphogenèse et Antigénicité du VIH et des Virus des Hépatites)

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

ICOA Institut de Chimie Organique et Analytique
MAVIVH Morphogenèse et Antigénicité du VIH et des Virus des Hépatites

Help of the ANR 93,074 euros
Beginning and duration of the scientific project: November 2020 - 12 Months

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