The Ebola virus, a type of filovirus, was first identified in 1976 resulting in a 50 to 90 percent mortality rate. Since then, five significant outbreaks have plagued West Africa, and the potential to weaponize the virus is a threat too dangerous to ignore. Now the Defense Threat Reduction Agency’s Joint Science and Technology Office, the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) Therapeutic Development Center and the Joint Program Executive Office for Chemical and Biological Defense (JPEO) have developed a promising antiviral drug therapy to address this concern.
February 7, 2017 - The JSTO-USAMRIID team tested the molecule’s effectiveness against a lethal Ebola virus infection in non-human primates. Administering GS-5734 resulted in 100 percent protection, whereas all controlled animals succumbed to the Ebola virus. (Courtesy image by Defense Threat Reduction Agency's Chemical and Biological Technologies Department)
The antiviral drug may save countless warfighter and civilian lives, treating those who encounter weaponized or naturally occurring filoviruses. The treatment, GS-5734, is a small molecule prodrug analogue of adenosine, which has broad-spectrum capabilities to fight a variety of filoviruses such as Ebola, Marburg and Bundibugyo.
Researchers discovered the compound’s unique characteristics while screening a library of small molecules when searching for those that had the capability to prevent viruses from encoding their lethal genome sequence into RNA.
The JSTO-USAMRIID team tested the molecule’s effectiveness against a lethal Ebola virus infection in non-human primates. Administering GS-5734 resulted in 100 percent protection, whereas all controlled animals succumbed to the Ebola virus. The drug, when administered once daily beginning three days after infection for 12 days, worked quickly (within two hours) and stayed within the subject’s system for a sustained period of time (14 hours). Both markers are important characteristics of an effective drug therapy.
In addition, the Ebola virus’ RNA showed no evidence of genetic changes, another positive attribute of the drug. Over the course of an infection, sometimes viruses mutate to avoid being eliminated by a drug therapy. However, during this experiment, the Ebola virus’ RNA showed no evidence of genetic changes, another positive attribute of the drug. Overcoming potential drug resistance is a major success in the battle to reduce biological threats to the warfighter.
Engagement with the Food and Drug Administration has guided clinical and non-clinical development of the molecule’s drug applications. Currently, intravenous administration of GS-5734 is undergoing evaluation to assess clinical safety and pharmacokinetics, or how drugs move within the body. This research will also help determine the optimal use of GS-5734 as a therapeutic agent in acute, chronic and re-emerging disease scenarios.
GS-5734’s broad-spectrum antiviral activity and amenability to large-scale production prompted the transfer of the project from the JSTO research phase to advanced development, overseen by the JPEO. Following the tenets of the Better Buying Power 3.0 initiative, this project incentivizes productivity and innovation between industry and government to provide the first small molecule to treat Ebola disease in patients, post exposure.
The development of GS-5734 creates a new therapeutic for warfighter and civilian populations, providing protection from either the intentional release of, or naturally occurring, filoviruses such as Ebola. For more information, visit the Nature article, “Therapeutic Efficacy of the Small Molecule GS-5734 Against Ebola Virus in Rhesus Monkeys.”
By U.S. Army LTC Jurandir Dalle Lucca
Defense Threat Reduction Agency's Chemical and Biological Technologies Department
Provided through DVIDS
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