Séminaire CIRI : Dr. Nathalie GRANDVAUX

Nathalie GRANDVAUX (Université de Montréal ; Faculté de médecine - Département de biochimie et médecine moléculaire) 

Titre séminaire: « Development of host-targeting broad spectrum antivirals against RNA viruses: a missed opportunity before the COVID-19 pandemic - Our search for new targets »

Résumé: As we learned the hard way with the COVID-19 pandemic, we urgently need broad spectrum antivirals and anti-inflammatory drugs to treat severe pathogenesis induced by emerging viruses but also seasonal viruses, such as Respiratory Syncytial virus and Influenza, that are life threatening and a major burden on our healthcare system. Our research program aims at identifying host mechanisms that could serve as targets for the development of new drugs. Specifically, our aim is to uncover novel regulatory mechanisms that determine how airway epithelial cells mount an interferon-mediated antiviral response, as well as a proinflammatory response. This first line of response is determinant of virus-induced pathogenesis. An appropriate intensity and duration of this response is essential to achieve the most appropriate response for efficient fighting of the infection without generation of side effects, including tissue damage. With the identification of key regulatory players in the past 20 years, current research focus has moved towards the elucidation of the molecular mechanisms allowing a fine and stringent regulation of the signaling pathways. Our group explores several transdisciplinary lines of research. In particular, we pioneered the discovery of the key role of the redox metabolism in the control of the interferon-mediated antiviral and proinflammatory responses. Our research led to identification of the role of ROS-producing NADPH oxidases. We now use biochemical and proteomics-based approaches to determine how ROS modify the host proteome via protein oxidation. We uncovered specific redox post-translational modifications of cellular adaptors that determine the fate of the interferon response. This basic knowledge is an essential part of an international effort to identify therapeutic targets for the development of broad-spectrum antivirals targeting the host for the treatment of emerging or seasonal high-incidence respiratory viruses not only in Canada, but also around the world. It also founds applications in the understanding of autoinflammatory diseases, in which deregulation of antiviral mechanisms is observed.

Hôte : Lionel Condé (REVE team)