Project III: Synthesis of small molecules targeting the inhibition of viral replication by the IFN pathway
Type I interferons play a central role in the establishment of an innate immune response against viral infections and tumor cells. This host response, upon viral infection, usually results in a control infection and elimination of the pathogen. This mechanism relies on signaling pathways and is largely based on the synthesis and secretion of interferon by cells infected via transcription factors activation cascade (IRF3 / 7, NF-KB ...) and will spread a signal to induce an antiviral state in neighboring cells. Recognition of IFN-α / β receptor by the IFNAR1 / 2 triggers an activation signal by the JAK / STAT pathway, to propagate to the nucleus to activate transcription of hundreds of genes (ISG) having antiviral or immunomodulatory properties. However, for many viruses (HCV, HBV, HIV, HSV, Vaccine, Dengue, Ebola), the IFN signaling pathway is counteracted at multiple levels, both in terms of its induction that these effectors. They can exert their exhaust strategy by inhibiting the synthesis of type I IFN and / or by inhibiting the response to type I IFN. Thus, the recent characterization of the receptors involved in the recognition of pathogens, they activate signaling pathways, revolutionized our understanding of innate immunity and have revived interest in the design of small molecules.
We aims to design and synthesize small molecules for inhibition of viral proteins responsible for blocking the way (IFN) as agonists of receptors (TLR , RLH .. ) and which could support the IFN response towards multiple pathogens.