Re-Tasking of Approved FDA Drugs for Iatrogenic Botulism Treatment: A Paired 3D-QSAR/Docking Approach.

Botulinum toxin is widely used in medicine for the treatment of spasticity and focal dystonia, for the treatment of chronic migraine, facial hemispasm, and facial aesthetic treatments. Generally, botulinum toxin treatment is a safe procedure when it is conducted by clinicians with expertise and local side effects are rare and transient; however, sometimes the adverse effects is due to the spread of the drug on nontargeted muscles or organs producing dry mouth, fatigue, and flu-like syndrome up to the signs of systemic botulism which appears to be more frequent in children treated for spasticity than in adults. In - silico 3D-QSAR and molecular docking have been employed to builds a structure-based model on selected potent known botulinum neurotoxin type A inhibitors and use it to screening the FDA database. Thirty molecules have been identified as possible light chain BoNT/A inhibitors. In this study, we applied a well establish ligand- and structure-based methodology for the identification of hit-compounds among a database of FDA-approved drugs. The identification of budesonide, protirelin, and ciclesonide followed by the other compounds can be a starting point for the investigations upon the selected compounds without going through the long and twisted way of drug approval.