SBIR-STTR Award

The primary challenge of anti-viral drug discovery in honey bees is the small number of compounds that can be screened. Drug hunters have so far screened maybe 20 candidates for Deformed wing virus. This number contrasts with the accepted principle of drug discovery that drugs are rare and discovery is unpredictable. Finding even one drug out of many thousands of compounds is considered a stroke of good fortune. There is now the opportunity to obliterate this barrier with an artificial intelligence approach that can identify "active" hit compounds at a rate up to 10000X higher than the physical high- throughput screening methods it augments. The plan is for Atomwise (atomwise.com San Francisco CA) to apply its artificial intelligence algorithms 10 million compound library and drug discovery expertise to Deformed wing virus. This approach is enabled by the USDA Bee Research Lab (Beltsville MD) which has led Deformed wing virus gene sequence and life cycle discovery efforts and has established efficient live honey bee physical drug screen. Granite Point Ventures(granitepv.com Greenbelt MD) establishing a Cooperative Research and Development Agreement with the Bee Research Lab leads the SBIR effort with its published honey bee drug discovery interest expertise in SBIR/STTR achievement project planning and commercialization of university and federal technologies. The anticipated result of Phase I is AtomNet virtual screening of up to 10 million compounds against at least one treatable part of the Deformed wing virus capsid 3-D structure. We anticipate the above activities will identify by artificial intelligence up to 70 small chemical compounds of high affinity for Deformed wing virus. This Phase I activity enables the larger Phase II effort of screening these 70 compounds in live infected bees for safety and efficacy at the Bee Research Lab.

Deformed wing virus is a leading cause of 40% annual honey bee colony loss. This loss putsat risk $34B worth of economic activity and high-value crops such as honey almonds blueberriesand apples. The goal of this SBIR Phase II project is to identify a lead chemical that can bedeveloped into a cure or treatmet for Deformed wing disease.Our approach is to use artificial intelligence algorithms to predict the binding of 10M smallchemicals to active sites of Deformed wing virus proteins. We expect this approach to increase by10000X the likelihood that physical screen of 90 chemicals will identify a chemical that can befurther developed through medicinal chemistry into a potent and safe inhibitor of Deformed wingvirus.The Phase I project has exceeded its goals. The team has in hand 90 chemicals of diversestructure ready for physical screen that are predicted to bind to the active site of the essentialDeformed wing virus 3C protease enzyme.The goals of this Phase II project are: for scientists at partner USDA-ARS Bee ResearchLab (Beltsville MD) to identify a lead chemical by way of physical screen of the 90 chemicals inlive honey bees and biochemical assay; through artificial intelligence and medicinal chemistry forpartner Atomwise Inc. (San Francisco CA) to further develop lead chemical potency and safety;and for Granite Point Ventures LLC the SBIR applicant and drug sponsor to achieve project goalsusing its scientific project management and commercialization expertise.