Background: Several studies have aimed to identify molecules that inhibit the toxic actions
of snake venom phospholipases A2 (PLA2s). Studies carried out with PLA2 inhibitors (PLIs) have been
shown to be efficient in this assignment.
Objective: This work aimed to analyze the interaction of peptides derived from Bothrops atrox PLIγ
(atPLIγ) with a PLA2 and to evaluate the ability of these peptides to reduce phospholipase and myotoxic
Methods: Peptides were subjected to molecular docking with a homologous Lys49 PLA2 from B. atrox
venom modeled by homology. Phospholipase activity neutralization assay was performed with BthTX-II
and different ratios of the peptides. A catalytically active and an inactive PLA2 were purified from the B.
atrox venom and used together in the in vitro myotoxic activity neutralization experiments with the peptides.
Results: The peptides interacted with amino acids near the PLA2 hydrophobic channel and the loop that
would be bound to calcium in Asp49 PLA2. They were able to reduce phospholipase activity and peptides
DFCHNV and ATHEE reached the highest reduction levels, being these two peptides the best that
also interacted in the in silico experiments. The peptides reduced the myotubes cell damage with a highlight
for the DFCHNV peptide, which reduced by about 65%. It has been suggested that myotoxic activity
reduction is related to the sites occupied in the PLA2 structure, which could corroborate the results
observed in molecular docking.
Conclusion: This study should contribute to the investigation of the potential of PLIs to inhibit the toxic
effects of PLA2s.