A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection
AbstractDeveloping drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound’s mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection. View Full-Text
- Supplementary File 1:
ZIP-Document (ZIP, 175 KB)
Share & Cite This Article
Bai, J.P.F.; Sakellaropoulos, T.; Alexopoulos, L.G. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection. Toxins 2017, 9, 99.
Bai JPF, Sakellaropoulos T, Alexopoulos LG. A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection. Toxins. 2017; 9(3):99.Chicago/Turabian Style
Bai, Jane P.F.; Sakellaropoulos, Theodore; Alexopoulos, Leonidas G. 2017. "A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection." Toxins 9, no. 3: 99.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.