Development of novel isoflavone drugs as broad spectrum antivirals

开发新型异黄酮药物作为广谱抗病毒药物

• 批准号: 9043719
• 负责人: Kristin M Bedard
• 金额: $ 75.78万
• 依托单位: KINETA, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-22 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9043719
• 关键词: ADME Study; Animal Model; Antiviral Agents; Antiviral Response; Antiviral Therapy; Back; Biochemical; Biological Assay; Biological Availability; Body Weight decreased; Cells; Characteristics; Chemicals; Clinical; Coronavirus; DNA Viruses; Data; Dengue Virus; Development; Dose; Drug Kinetics; Drug or chemical Tissue Distribution; Drug resistance; Ebola virus; Evaluation; Exhibits; Flavivirus; Frequencies; Genetic; Goals; Immune response; In Vitro; Infection; Influenza; Isoflavones; Lead; Mediating; Metabolic; Modification; Mus; Natural Immunity; Nature; Oral; Organ; Pathogenesis; Permeability; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Pre-Clinical Model; Property; Qualifying; RNA Viruses; Resistance; Respiratory Syncytial Virus Infections; Safety; Scientist; Solubility; Specificity; Staging; Therapeutic; Therapeutic Index; Therapeutic Intervention; Toxicology; Universities; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Virus Replication; Washington; West Nile virus; Work; aqueous; base; drug candidate; drug development; drug discovery; drug mechanism; efficacy testing; fighting; in vivo; influenzavirus; innovation; lead series; meetings; mouse model; novel; pathogen; pre-clinical; product development; public health relevance; resistant strain; respiratory virus; scaffold; small molecule; viral DNA; viral resistance; virology

 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.