NCATS funds collaboration initiative aimed at repurposing antimalarial to combat Ebola virus

Texas Biomedical Research InstituteNov 10 2016

The National Center for Advancing Translational Sciences (NCATS) recently awarded $596,533.00 to Collaborations Pharmaceuticals, Inc. (CPI) to initiate a partnership with Texas Biomedical Research Institute aimed at repurposing an antimalarial for use against the Ebola virus.

Since 2014, the outbreak of the Ebola virus in West Africa has resulted in 28,657 suspected cases and 11,325 deaths (according to WHO statistics) and highlighted the need for broad-spectrum antiviral drugs for this and other emerging viruses. Data from a published large scale high throughput screen performed by SRI International and Texas Biomedical Research Institute was used to create machine learning models that identified 3 compounds active against the virus in vitro (in a lab, outside of a living organism). This earlier work had suggested that antimalarial compounds, as well as other classes of approved drugs could be of interest for repurposing.

"We used Bayesian machine learning models based on the earlier published dataset to screen a library of more than 2000 drugs and drug-like molecules, which then lead to the discovery that of the 3 compounds identified, a relatively new antimalarial called pyronaridine, approved in Europe had promising activity in vitro and could be worthy of testing in vivo (in a living organism) against the Ebola virus" said Sean Ekins, CEO CPI.

"My lab has screened thousands of compounds against Ebola virus," said Dr. Robert Davey, Interim Chair of Texas Biomed's Department of Virology and Immunology. "This particular compound, pyronaridine, is promising because it is already an approved drug in Europe, has been used in thousands of patients and may have favorable molecular properties that could speed up its transition to clinical testing. We do not currently know the target of the three compounds and there is still considerable research needed."

Dr. Davey is interested in understanding how viruses like Ebola virus penetrate the cell membrane and establish infection. In addition, Dr. Davey's laboratory has developed safe, efficient, high-throughput screening techniques for Ebola virus and performs contract work on testing drugs and compounds against Ebola virus infection in the biosafety level-4 maximum containment laboratory. This work has resulted in exciting findings towards potential drug candidates to combat Ebola virus.

"This collaboration involves Texas Biomedical Research Institute, Stanford Research International and Rutgers University, and we are very grateful to NCATS for funding so we can illustrate how computational approaches can be used to repurpose drugs already approved for other uses and instead use for neglected diseases" said Dr. Ekins.