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Evaluation of Ebola Virus Inhibitors for Drug Repurposing
Peter B Madrid1, Rekha G Panchal2, Travis K Warren2
1Biosciences Division, SRI International , 333 Ravenswood Avenue, Menlo Park, California 94025, United States.
ACS Infectious Diseases
|September 14, 2016
Summary
Researchers screened FDA-approved drugs for Ebola virus (EBOV) activity. Chloroquine (CQ) showed reproducible efficacy in mice, but drug repurposing for EBOV presents challenges.
Area of Science:
- Virology
- Pharmacology
- Drug Discovery
Background:
- Ebola virus (EBOV) poses a significant public health threat, necessitating rapid development of countermeasures.
- Drug repurposing offers a potential strategy for quickly identifying effective treatments against emerging infectious diseases.
Purpose of the Study:
- To systematically screen FDA-approved drugs for in vitro antiviral activity against EBOV.
- To evaluate the in vivo efficacy of promising drug candidates in animal models.
Main Methods:
- Systematic in vitro screening of FDA-approved drugs against EBOV.
- Dose-response assays to quantify antiviral activity and cytotoxicity.
- In vivo efficacy studies in mouse and guinea pig models using selected drug candidates.
Main Results:
- Seven compounds, including chloroquine (CQ), azithromycin, and amiodarone, showed in vitro activity.
- CQ demonstrated reproducible efficacy in a mouse model of EBOV infection.
- Azithromycin and CQ showed toxicity in guinea pigs, and neither improved survival in this model.
Conclusions:
- Drug repurposing for EBOV is feasible but presents specific challenges, including variable efficacy and toxicity across models.
- Careful evaluation of approved drugs is crucial for developing rapidly deployable countermeasures against viral pandemics.
