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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.
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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)
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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
Copyright 2017
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