US researchers have found 53 existing approved 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 which the study shows to hinder infection by an Ebola virus model are several cancer drugs, antihistamines and antibiotics, and among the most effective at keeping the virus out of human cells are microtubule inhibitors used to treat cancer, say the researchers, from the US National Institutes of Health (NIH) and the Icahn School of Medicine, who have published their findings in the Nature Press journal Emerging Microbes and Infections.
Other categories that block viral entry include estrogen receptor modulators used against cancer and serotonin reuptake inhibitors used to treat depression, they add.
There is no approved treatment for Ebola virus infection, and the estimated mortality rate of the current outbreak is nearly 70% in many areas, say the researchers. Antibody-based therapy, such as Mapp Biopharmaceuticals’ ZMapp, has proven effective in animal studies and has been used in the treatment of a few patients, but it has not been confirmed in clinical trials, it is very expensive to make and it is in short supply.
Ebola vaccine trials are also getting underway, but vaccines will not be available for some time.
The researchers used a miniaturised, high-speed technology to screen through sample libraries of 2,816 compounds already approved by the US Food and Drug Administration (FDA) for other uses. Their assay was designed to identify compounds that blocked the ability of the Ebola virus to enter and infect human cells by at last 50%.
While fully-intact Ebola virus is a biosafety level (BSL) 4 pathogen and dangerous to work with, the researchers 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 drug blocked the entry of Ebola-like viral particles into cells as measured by fluorescence. These Ebola mimics can be studies in a BSL-2 facility, making them much safer to work with, they say.
Some of the 53 drugs found to block Ebola virus-like particles from entering human cells have been shown by previous studies to counter Ebola lifestyle 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, say the researchers.
“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.
“Many of the compounds identified in this study promise to become lead compounds in near-future drug development efforts studies targeting this virus,” he added.
