San Antonio researchers are preparing to test potential antiviral compounds against filoviruses, a family of deadly viruses that includes the rare Bundibugyo virus driving the current Ebola outbreak in Central Africa.
Scientists at Texas Biomedical Research Institute — home to one of few laboratories in the U.S. equipped to study dangerous pathogens like Ebola — collaborated with Southwest Research Institute, where chemists used AI-powered software to identify over 20 antiviral drug candidates.
More than 80 cases of Ebola have been confirmed in the Democratic Republic of Congo. But the outbreak is likely much larger, with health officials putting the suspected number of cases at 750 and 177 suspected deaths, according to the latest numbers from the World Health Organization.
The outbreak is driven by the Bundibugyo virus, involved in just two previous Ebola outbreaks since 1976. No approved vaccines or therapeutics exist for the Bundibugyo strain, making potential broad-spectrum antivirals especially relevant.
“We have a couple very strong candidates that would serve as broad spectrum against all filoviruses,” Texas Biomed virologist Olena Shtanko said. “They would target the absolutely critical part of the virus replication step.”
In the coming months, researchers will test the molecules in laboratory cells and rodents, potentially paving the way for further studies. But it’s unclear whether any of the compounds will ultimately prove safe and effective enough for human use, and whether they could be developed quickly enough to help contain the current outbreak.
“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 drug discovery technology known as Rhodium.
A unique Ebola outbreak
In mid-May, illnesses affecting healthcare workers in the Democratic Republic of Congo were identified as the Bundibugyo virus, one of four types of Ebola virus that cause severe disease in humans.
Bundibugyo only accounts for two previous Ebola outbreaks, in 2007 and 2012, both relatively minor outbreaks infecting fewer than 150 people. The research on Ebola has thus been mostly focused on the Zaire and Sudan viruses, responsible for the majority of outbreaks.
“Bundibugyo was not on the radar,” Shtanko said.
The World Health Organization declared the outbreak as a public health emergency of international concern, which mobilizes funding and international resources to contain the spread of the disease. Officials have not declared the outbreak a pandemic and said the risk of global spread remains low.
“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,” said Larry Schlesinger, president and CEO of Texas Biomed. “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.”
Ebola was first reported in Sudan in 1976 and has caused dozens of outbreaks in Africa since then. The most severe outbreak occurred from 2013-2016, infecting over 28,000 people across ten countries and killing over 11,000. Another outbreak from 2018-2020 killed over 2,000.
Two licensed vaccines exist against the Zaire virus. But these vaccines have not been tested against Bundibugyo.
“The Bundibugyo virus is different enough,” Shtanko said. “The immunity that was generated through vaccination to Ebola virus is probably not going to recognize Bundibugyo.”
San Antonio researchers search for broader treatments
Shtanko’s research has shed light on the mechanisms behind how the Ebola virus and other filoviruses enter cells and proliferate, laying groundwork for future vaccination and therapeutic development efforts.
Texas Biomed and SwRI’s partnership on Ebola virus research began in 2016, made possible by a contract award from the Defense Threat Reduction Agency, which operates under the U.S. Department of Defense.
Over the past two years, the research institutes have worked together to test one antiviral molecule known as “M7.” This molecule and others like it disrupt the viral replication process, which occurs once the virus has entered the cell.
Unlike vaccines and monoclonal antibodies that target the virus itself, these tiny molecules aim to block the machinery inside our cells that the Ebola viruses hijack to replicate.
By targeting cellular “replication hubs,” Shtanko said, the molecules offer broader protection against any of the viruses that rely on the same cellular process, including filoviruses and potentially others.
Another pathway the researchers are exploring is blocking the ability for the virus to “uncoat itself” and release its genetic material once inside the cell.
Although M7 showed promise initially, it didn’t have the right properties for use in drug manufacturing. SwRI conducted internally-funded research to identify more than 20 related compounds with more stable properties using its Rhodium software and large language model 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,” SwRI president and CEO Adam Hamilton said.
Because the drug candidates disable parts of our cells, researchers will have to find a sweet spot: a high enough dose to achieve the benefits without damaging our cells and causing toxicity.
In the coming months, Shtanko will test the molecules in laboratory settings and rodents to gauge toxicity.
If the results are positive, the next step would be testing the most promising candidate against filoviruses at Texas Biomed’s BSL4 containment lab. Preclinical testing on the institute’s primate population or guinea pigs could follow.
“We will evaluate toxicity in mice. Once we figure out that the drug or drugs are non-toxic, which is not guaranteed, then we will plan for a BSL4 experiment involving the live virus,” Shtanko said.
Texas Biomed is currently constructing an additional biocontainment lab, as part of a $210 million campus expansion.
Ultimately, Shtanko suspects that a cocktail of different antivirals could be combined, targeting different stages of the infection process. Various labs are working on other pathways, too, she said.
But nothing is guaranteed — there are several ways that the drug candidates might not pan out, Shtanko cautioned. Still, she remains optimistic.
“I have very high hopes,” she said. “People have been hunting down (small-molecule antivirals) for a while now. We have some experimental drugs but none of them seem to be working really well. So people wonder if it’s even possible. I do think so.”
