SwRI is working with Texas Biomedical Research Institute (TBRI) on two drug development projects targeting the Ebola virus. The Defense Threat Reduction Agency (DTRA) awarded the team a three-year,
$9.1-million contract to combine two available medications, while the National Institute of Allergy and Infectious Diseases (NIAID) awarded a three-year, $3.7-million grant to modify a compound used to treat high blood pressure in China.
Hemorrhagic fevers like Ebola have very low survival rates. No proven treatments for these viruses mean outbreaks can result in fatalities as high as 90 percent.
“We are at the forefront of rapidly developing and fielding these new treatments,” said Dr. Joe McDonough, director of SwRI’s Pharmaceuticals and Bioengineering Department. “We are taking a unique approach to repurpose existing or develop novel therapeutics that can be enhanced to target emerging biothreats like Ebola.”
For DTRA, SwRI will use core pharmaceutical capabilities to create a more bioavailable, or more easily absorbed, formulation of cepharanthine (CEPN). CEPN is a Japanese drug that has been safely used for more than 40 years to treat a wide range of illnesses. In screening for chemical compounds that could potentially fight an Ebola infection, Texas Biomed scientists discovered CEPN was effective at combatting the Ebola virus but required very high doses. This new formulation of CEPN will be combined with chloroquine, a drug used to treat malaria.
“We had found that chloroquine, a drug traditionally used to treat malaria, also stopped the Ebola virus, but again, at very high doses,” said Dr. Robert Davey, scientist and chair of the department of Virology and Immunology at Texas Biomed. “After reading that chloroquine combined with cepharanthine had a synergistic effect in treating malaria, we put two and two together. We want to test the idea that this combination could create a powerful Ebola virus inhibitor cocktail. Our collaboration with McDonough’s group at SwRI and funding from DTRA gives us the means to test the idea.” Texas Biomed will conduct efficacy testing of the formulations in its state-of-the-art Biosafety Level 4 Laboratory.
For NIAID, SwRI is modifying the compound tetradrine, based on TBRI research showing the compound can inhibit Ebola infections. Tetrandrine, a drug derived from an Asian herb, is banned everywhere but in China because it can cause blood pressure to drop precipitously. The compound has been found to improve the survival of mice infected with Ebola, but equivalent doses could be toxic for humans. The SwRI-TBRI team is looking at ways to improve the drug’s efficacy while overcoming danger-ous side effects.
“We expect these efforts will provide significant new countermeasures to improve readiness to treat Ebola,” McDonough said.
SwRI is the primary contractor on both programs with TRBI providing virology expertise and drug efficacy evaluations. Both organizations are part of the Vaccine Development Center of San Antonio (VDCSA). The global nature of epidemics emphasizes the importance of international collaborations, and VDCSA coordinates these efforts for the region.