A number of clinical observations from early work by a chinese team followed by those of a Pitié Salpétrière and Institut Pasteur team revealed that the incidence of COVID-19 is higher in non-smokers than smokers. From this observation, we hypothesis that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of COVID-19 infection and might represent a target for its prevention and control. As a consequence, we propose nicotinic orthosteric and/or allosteric agents as a possible therapy for SARS-CoV-2 infection To explore the mechanism of action this type of compound against COVID-19 in vivo, we will use the model of SARS-CoV-2 hamster infection. This project is funded by the COVID-19 task force grant: NicoCovid.
To widely comprehend the immune response and the involvement of specific metabolic pathways in different organs during SARS-CoV-2 infection and the effects caused by nicotinic agents, we propose to perform a paired RNAseq study based on three main organs: i. the lungs, considered as the main target organ of Covid-19, ii. the olfactory bulbs, since these structures are in close contact with the nasal cavity and presents a striking innate immune response during the infection (manuscript in preparation), and iii. the brainstem, where the respiratory and the cardiovascular centers are localized, and where most of the cranial nerves emerge, including the vagus nerve involved in the cholinergic anti-inflammatory pathway. The results of this project will provide clues to understand how nicotine derivatives act against COVID-19 and help identify preferred targets of these molecules.
