As global Ebola crisis continues to evolve, researchers are hard at work to find effective antivirals to treat the disease. Even though there are no Ebola-specific drugs approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMEA), scientists suggest a few compounds already out there could help against the Ebola virus.
Last year, two independent studies have identified antimalarial drugs and selective estrogen receptor modulators (SERMs) as promising agents against different Ebola virus’ strains; several of these are now being evaluated in animal models. Building on these findings, a new study published this month in F1000Research suggests some FDA-approved drugs could share a common mechanism of targeting Ebola, and a number of additional compounds should be evaluated in the lab.
Two different drug classes, antimalarials and SERMs, were taken through a computational analysis to construct a pharmacophore – a virtual model that combines features of different drugs. A pharmacophore based on amodiaquine, chloroquine, clomiphene and toremifene – FDA-approved drugs most relevant to the Ebola treatment – shows how structurally diverse drugs might target the same site of the virus. The model can be used to screed hundreds of FDA-approved compounds, which are evaluated by the Fit Value to the pharmacophore.
The study confirmed that SERMs and antimalarial aminoquinolines in fact share a number of structural features, which suggest a common mechanism or target within the virus. Moreover, a number of other FDA drugs were identified as good candidates for future in vitro studies. Of these, estradiol and dibucaine have already been described as effective against Ebola in in vitro tests.
Amodiaquine and chloroquine were also find to overlap with ligands bound within VP35 protein of the virus. VP35 has been identified as a multifunctional virulence factor of Ebola, and is thought to block the immune system’s interferon response. This suggests these and other drugs with similar binding affinity could be highly effective in reducing the infectious potential of the disease.
Moreover, the relative low cost and high availability of amodiaquine and chloroquine should prompt their further exploration in the laboratory setting.
Interestingly, both of these drugs have also been reported as effective against other viruses, including human coronavirus and SARS. This potential could be explored with their structural analogs and additional FDA-approved compounds.
Exploring the potential of drugs that are already available and ready-to-go would provide a much-required boost to finding the Ebola cure, as well as help prepare for outbreaks of other viruses that are yet to come.
The research was published as part of Ebola article collection at F1000Research, which can be accessed here.
Written by Eglė Marija Ramanauskaitė