Deciphering the role of RHA Helicase in the replication of RNA viruses: mechanism of action and targeted inhibition – VIR2RHA

The recent SARS-CoV-2 pandemic has highlighted the need to develop new antivirals against RNA viruses that are responsible for more than a third of new emerging or re-emerging infections. As many RNA viruses use cellular helicases during their infectious cycle, these proteins have become promising therapeutic targets. VIR2RHA is a collaborative research project aimed at developing RHA inhibitors to effectively fight against a broad spectrum of RNA viruses. Thus, using drug design approaches, we have developed new original molecules which bind specifically to RHA, which are non-toxic and which demonstrate broad-spectrum antiviral properties in vitro against Chikungunya virus (CHIKV), the virus Dengue fever (DENV), influenza virus (IAV), human immunodeficiency virus type -1 (HIV-1), T-cell leukemia virus type 1 (HTLV-1) and also the SARS-CoV-2 responsible for the COVID-19 pandemic. In the VIR2RHA project, our objectives are to study the mechanisms of action of our inhibitors in order to continue their preclinical development. This program is also designed to elucidate the proviral functions of RHA in the infectious cycle of these RNA viruses. Our program is part of the pandemic preparness action and adapts to the axes "Life, Health and Well-being" and "Medical innovation, Nanotechnologies, Regenerative medicine, Innovative therapies and vaccines" of the ANR 2022 call