LONDON: In a big boost to the global fight against the deadly Ebola virus, scientists have found 53 existing drugs that may keep the Ebola virus from entering human cells, a key step in the process of infection.
Among the better known drug types shown to hinder infection by an Ebola virus model include several cancer drugs, antihistamines and antibiotics.
Among the most effective at keeping the virus out of human cells were found to be microtubule inhibitors used to treat cancer, according to researchers at the Icahn School of Medicine at Mount Sinai and the National Institutes of Health (NIH).
The next step is to test 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.
At present, there is no approved treatment for Ebola virus infection and the estimated mortality rate of the current Ebola outbreak is nearly 70%.
Antibody-based therapy (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.
Ebola vaccine trials are getting underway as well, but vaccines will not be available for some time.
“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 Adolfo Garcia-Sastre from Icahn School of Medicine.
“Any of the compounds identified in this study promise to become lead compounds in near-future drug development efforts studies targeting this virus,” he added.
What the team has done is sift through sample libraries of 2,816 compounds already approved by the US Food and Drug Administration for other uses. They used a miniaturized, high-speed technology to screen through.
Their assay was designed to identify compounds that blocked the ability of the Ebola virus to enter and infect human cells by at least 50%.
While fully intact Ebola virus is a biosafety level (BSL) 4 pathogen and dangerous to work with, 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.
When they inserted a fluorescent reporter protein in this virus-like shell, their test became capable of high-speed screening to see which drugs blocked the entry of Ebola-like viral particles into cells as measured by fluorescence. These Ebola mimics can be studied in a BSL-2 facility, making them much safer to work with.
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.
