Development of novel isoflavone drugs as broad spectrum antivirals

DESCRIPTION provided by applicant Kineta has discovered a novel class of broad spectrum small molecule antivirals that function through a host directed mechanism These compounds have demonstrated an innovative mechanism of action and target several high priority pathogens that are commercially valuable The lead chromenone based candidates have potency in the nM range inhibit multiple viruses including influenza coronavirus West Nile ebola and dengue virus in vitro and in animal models have an attractive pharmacologic profile and are well tolerated in vivo In this application we will perform lead optimization and preclinical development of the lead series The major milestone of the project is to select one or more nominated drug candidates for formal IND enabling development towards an oral therapeutic for broad respiratory viral infections Drug treatment to stimulate the host innate immune response is increasingly appreciated as a strategy for therapeutic intervention and has the potential to redefine the paradigm of antiviral drug development The need for effective antivirals is great and our approach to stimulate innate immunity in the presence of diverse viral countermeasures has yielded promising leads that are effective against a broad range of RNA and DNA viruses We have assembled a highly qualified development team that includes the Kineta scientists responsible for the antiviral discovery work and Prof Michael Gale Jr of the University of Washington an expert in innate immunity and the antiviral response PUBLIC HEALTH RELEVANCE We have utilized a unique drug discovery strategy to identify potential new antiviral drugs that work by activating a faster more potent immune response to fight off virus infection Our goal is to develop lead candidates as oral antiviral drugs for a varety of viruses including influenza virus RSV coronaviruses and flaviviruses The lead drugs have shown broad spectrum activity and in vivo efficacy against broad respiratory viruses The confirmed drug mechanism of action is an innate immune response and they are predicted to be more effective and less prone viral resistance than conventional direct acting therapeutics