Inhibition in vivo of the activity of botulinum neurotoxin A by small molecules selected by virtual screening

► We did virtual screening of about 1 million compounds vs BoNT/A substrate binding pocket. ► Five compounds that had favorable fit were tested in a mouse protection assay. ► Two compounds bound into the binding site, protected all mice from lethal toxicity. ► Two compounds protected 75%, and one 25%, of the mice against a lethal toxin dose. ► Virtual screening helps to identify likely toxin inhibitors for more improvement.