New AI tools identify potential drugs for rare Ebola virus

Recent advances in artificial intelligence have enabled Southwest Research Institute (SwRI) to identify nearly two dozen antiviral compounds that could potentially treat a rare species of Ebola virus (Bundibugyo virus) currently affecting the Democratic Republic of Congo.

According to the World Health Organization, 516 suspected cases and 33 confirmed cases of disease caused by the Bundibugyo Ebolavirus have resulted in as many as 133 deaths. Bundibugyo virus, named for a region in Uganda where the species was first identified in 2007, kills up to 40% of infected people.

"We stand ready to support the biomedical community with rapid research and development of antiviral drugs as global health professionals respond to the latest outbreak," said Dr. Jonathan Bohmann, lead developer of SwRI's Rhodium™ molecular docking software designed to virtually screen drug compounds. "Our AI and machine learning tools help to quickly identify drug candidates that are the most likely to work in not only a high-value biocontainment environment, but also in the human body."

The SwRI research is part of a decade-long collaboration with the Texas Biomedical Research Institute (Texas Biomed) where SwRI designs and formulates candidate vaccines and antivirals that Texas Biomed tests on live viruses in its state-of-the-art Biosafety Level 4 (BSL4) Laboratory.

The current Ebolavirus outbreak is a clear reminder that biomedical research is not only a public health priority, but also a matter of national and global security. Sustained investment in infectious disease research, along with the development of vaccines and therapeutics, is essential to ensuring that we are prepared to contain outbreaks before they become broader global threats."

Larry Schlesinger, president and CEO of Texas Biomed

The Ebola virus is rare with occasional outbreaks in equatorial Africa often linked to native fruit bats. While there are some antiviral treatments for other virus species, there are no approved drugs for Bundibugyo Ebolavirus.SwRI and Texas Biomed began collaborating on Ebola virus research in 2016 with a contract award from the Defense Threat Reduction Agency (DTRA) to combine two available medications and test the resulting combination drug therapy against the Ebola virus. Over the past two years, Texas Biomed worked with SwRI to test the small molecule "M7," a potent inhibitor of another species, Zaire Ebolavirus. M7 is a host-directed antiviral, which means it should work on a larger number of virus types than direct-acting antivirals, which are more common.

While the M7 compound showed promise in Texas Biomed's lab testing, it did not have the right properties for scale-up as an approved drug for manufacturing, Bohmann said. However, SwRI recently conducted internally funded research to identify more than 20 related compounds with more stable properties using SwRI-developed Rhodium software in conjunction with large language model (LLM) AI tools.

"Our internally funded R&D investments give us the ability to quickly launch research projects, like this one, to speed up the process of getting useful therapies where needed as soon as possible," said Adam Hamilton, president and CEO of SwRI.

The project, known as Generative Approaches for Molecular Encodings (GAMES) LLM, generates Simplified Molecular Input Line Entry System (SMILES) strings. SMILES is an industry standard system that represents the structure of molecules using a short series of text characters to facilitate storage, retrieval and modeling.

The AI-driven approach using the SwRI-developed GAMES language model prioritized the selection of precursors to rapidly synthesize 18 novel analogs to screen against the Bundibugyo species. The team factored in supply chain considerations, focusing on a domestic source of building block precursors to encourage a rapid response. Texas Biomed will screen the compounds in the coming weeks.

"Now that SwRI has identified more of these meaningful compounds, we can test against the latest virus and provide accelerated results," said Dr. Olena Shtanko, a virologist at Texas Biomed. "The impacts of this work are overwhelmingly important, and we are eager to support the research community through our trusted collaboration."

SwRI and Texas Biomed are independent nonprofits based in San Antonio, Texas, a hub of biomedical innovation. SwRI performs applied R&D across multiple technical disciplines and industry applications. Texas Biomed is dedicated to protecting the global community from infectious disease and has long been at the forefront of Ebola virus research, helping advance critical countermeasures against one of the world's deadliest pathogens.