Computationally guided drug repositioning: QSAR-based Virtual Screening of Macrolides for Schistosomiasis

Macrolides are a class of antibiotics possessing a macrocyclic lactone ring linked to an amino sugar. They present antimicrobial, anti-HIV, immunomodulating and antiparasitic activities.1 As macrolides usually show good safety and pharmacokinetic profiles, they can be good starting points for the discovery of new uses for old drugs, known as drug repositioning.2 Thus, we performed a QSAR-based virtual screening to predict the activity of 3,965 macrolides from Integrity database against the Schistosoma mansoni thioredoxin glutathione reductase (SmTGR)3, a validated target for schistosomiasis. Through the QSAR-based virtual screen, eight macrolides predicted as active were selected to perform the molecular docking in SmTGR. Three of these macrolides, sorangicin A, A-349079-S1 and amphidinolide H1 showed the best molecular interactions with SmTGR, interacting with important amino acids residues (K124, K128 and, V593) from the allosteric site of SmTGR. Our next steps involve the experimental validation of the selected macrolides against SmTGR.