Screening of existing drugs finds 53 that may prevent Ebola virus
6 January 2015
A study led by researchers at the Icahn School of Medicine at
Mount Sinai and the US National Institutes of Health (NIH) has found
53 drugs approved for other uses that may keep the Ebola virus from
entering human cells, a key step in the process of infection.
The study was published in the journal Emerging Microbes and
Among the better known drug types shown to hinder infection by an
Ebola virus model are several cancer drugs, antihistamines and
antibiotics. Among the most effective at keeping the virus out of
human cells were microtubule inhibitors used to treat cancer.
“In light of the historic and devastating outbreak of Ebola virus
disease, there is an urgent need to rapidly develop useful
treatments against Ebola infection, and our study results argue that
repurposing existing drugs may be among the fastest ways to achieve
this,” said lead author Professor Adolfo García-Sastre of the Icahn
School of Medicine at Mount Sinai in the US.
“Many of the compounds identified in this study promise to become
lead compounds in near-future drug development efforts studies
targeting this virus,” said Prof García-Sastre.
There is no approved treatment for Ebola virus infection, and the
estimated mortality rate of the current Ebola outbreak is nearly 70%
in many areas. Antibody-based therapy (eg ZMapp) has proven
effective in animal studies, and has been used for the treatment of
a few patients, but has not been confirmed in clinical trials. It is
also expensive to make and in short supply as it requires growing
large quantities of genetically altered tobacco plants. Ebola
vaccine trials are getting underway as well, but vaccines will not
be available for some time.
“NCATS is all about getting more treatments to more patients more
quickly, and this is never more urgent than in the case of a public
health emergency like Ebola,” said Christopher P. Austin, MD,
Director of the National Center for Advancing Translational Sciences
(NCATS), part of the NIH, which also led the study. “This remarkable
team of scientists combined NCATS’ expertise in drug screening and
development with Mt. Sinai’s expertise in Ebola virology to rapidly
identified candidate treatments for Ebola infection.”
The research team used high-speed drug screening technology to
test sample libraries of 2,816 chemical compounds already approved
by the US FDA for other uses. Their test, or assay, was designed to
identify compounds that blocked the ability of the Ebola virus to
enter and infect human cells by at least 50%.
The team created a virus-like particle comprised of the Ebola
proteins (glycoproteins and matrix proteins) that enable the virus
to enter cells, but without many of the genes and proteins that make
the virus deadly.
They then inserted a fluorescent protein in this virus-like shell
so it could be optically tracked using high-speed screening
techniques. This showed which drugs blocked the entry of Ebola-like
viral particles into human cells.
While fully intact Ebola virus is a biosafety level (BSL) 4
pathogen and dangerous to work with, but the synthetic Ebola
virus-like particle is much safer to work with and can be studied in
a lower security BSL-2 facility.
The team’s screen yielded 53 drugs that block Ebola virus-like
particles from entering human cells. Along with the drug types
mentioned above, other categories that blocked viral entry included
estrogen receptor modulators used against cancer and serotonin
reuptake inhibitors used to treat depression. Some of the compounds
had been shown by previous studies to counter Ebola lifecycle steps.
Next steps include testing of the re-purposed drug candidates in
animal studies to see if useful doses against the virus come with
toxic side effects. If any of prove to be safe and effective, the
“government may opt to deploy them in the outbreak areas,” said Dr.