A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection

Area of Science:

• Computational biology
• Pharmacology
• Infectious disease research

Background:

• Bacillus anthracis produces lethal toxin (LT) and edema toxin (ET), causing severe disease.
• Developing effective treatments against anthrax toxins is a global health priority.

Purpose of the Study:

• To computationally screen existing drugs for their potential to counteract anthrax toxin effects.
• To identify novel therapeutic candidates for anthrax treatment.

Main Methods:

• Constructed molecular activity networks for LT, ET, and 474 drugs/compounds.
• Utilized gene expression profiles from Connectivity Map and Gene Expression Omnibus.
• Ranked drugs based on their network-based ability to reverse toxin-induced gene expression changes.

Main Results:

• Simvastatin and bepridil were computationally ranked high for reversing LT and ET toxicities.
• Other top-ranked drugs include fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine.
• Literature mining supported the potential protective roles of these identified drugs.

Conclusions:

• The identified drugs warrant further investigation as potential therapeutics against anthrax.
• These drugs could be explored as adjunct therapies alongside antibiotics for Bacillus anthracis infections.