A screen of approved drugs and molecular probes identifies therapeutics with anti–Ebola virus activity

Several FDA-approved drugs, including bepridil and sertraline, may be therapeutics against filovirus infections. Drug repurposing for Ebola virus The recent Ebola virus outbreak has highlighted the lack of therapies for filovirus infection. FDA-approved drugs serve as a source of medications with a proven safety record. Johansen et al. have now screened about 2600 FDA-approved drugs and molecular probes and found 80 that have some efficacy against Zaire ebolavirus in vitro. These drugs were mechanistically diverse, and several drugs, including a calcium channel blocker and an antidepressant, could protect against infection in a mouse model. Although new therapy development is ongoing, these repurposed drugs can rapidly move to human testing and may serve on the frontline against Ebolavirus infection. Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested ~2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration–approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.