Coronavirus

Coronaviruses are viruses generally responsible for infections of the epithelia of the digestive and respiratory systems in humans, but also in animals (mainly mammals and birds). The appearance of their viral particles with a crown of 20 nm high projections anchored in the viral membrane is characteristic of this family.

These projections called spikes are exclusively composed of protein S assembled into a homotrimer. The essential function of S is to recognize and bind to a specific receptor on the cell surface, this interaction being the first step in the entry of the virus into the target cell.

Our work mainly focuses on SARS-CoV-2, PEDV and to a lesser extent on other coronaviruses of veterinary interest.

Our scientific objectives are:

•   Improve understanding of the mechanisms underlying nasal cavity infection by SARS-CoV-2 at the cellular and molecular level (transient and persistent anosmia related to long term Covid symptoms).

We were able to show on the hamster model that infection with SARS-CoV-2 leads to massive desquamation of the olfactory epithelium ensuring the first step in the detection of odors in the nasal cavity, which explains the symptom of anosmia often seen in patients with COVID-19. We seek to understand the cellular origins of this phenomenon to develop therapeutic approaches as well as extend our results more generally to the relationships between respiratory viruses and the nasal cavity.

•   Develop anti-SARS-CoV-2 antivirals that block the entry of the virus

We have selected artificial proteins that bind with high affinity to the SARS-CoV-2 spike. Some of them are able to neutralize the virus in cell culture and are shown to have therapeutic properties of interest. This project is extended by the development of original strategies to increase the bioavailability of these antivirals in the nasal cavity. We anticipate that they will thus be able to effectively block horizontal transmission of the virus.

•   Identify coronavirus receptors of veterinary interest

Not all cell receptors for animal coronaviruses are identified. More particularly, the nature of the receptor for the avian infectious bronchitis virus as well as for the porcine epidemic diarrhea virus (PEDV), two coronaviruses having a strong economic impact in the avian and pork production sectors, have not been identified. We are developing experimental strategies to characterize them.

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