Broad-Spectrum Antivirals for Honey Bees in Crisis

In 2023, domestic beekeepers lost an estimated 48% of their colonies, higher than the average loss rate of 39.6%, since 2010. Colony losses threaten food safety and present a $250 million annual economic burden for commercial beekeepers. Therefore, there is an urgent need to ensure the safety of pollinators, which are essential for crop protection and ecosystem stability.RNA viruses, in particular Deformed Wing Virus, are a primary cause of honey bee mortality. RNA-dependent RNA polymerase (RdRp) controls the reproductionof all RNA viruses and does not exist in honey bee and mammalian cells. Therefore, it is a safe therapeutic target for developing broad-spectrum antivirals.Since no experimental structure is available for DWV RdRp, ELIXIDE built a new three-dimensional validated model using ColabFold. ColabFold internalizes the machine-learning approach and parameters used in AlphaFold. In Phase I, we aim to identify RdRp inhibitors of DWV using two independent state-of-the-art drug discovery platforms: 1) SilcsBio and 2) the artificial intelligence-accelerated platform OpenVS with the RosettaVS protocol. The safety and effectiveness of the hit molecules will be tested on honey bees. In Phase II, we will improve the drug-like properties of the leads and test their effectiveness at the colony level.The honey bee medicine market is valued around $135M in the US and $5B worldwide. As we aim to identify a broad-spectrum antiviral medication, we expect exponential revenue growth from the drug's broad applications in other veterinary and agricultural practices.