One of the deadliest
enzymes in the
snake venom is
l-amino acid oxidase (LAAO) which plays an important role in the pathophysiological effects during
snake envenomation. Some effects of this
enzyme on the human body are apoptosis, platelet aggregation,
edema,
hemorrhage, and cytotoxicity. Hence, inhibiting the
enzyme activity to reduce its degradation effects is of great medical and pharmacological importance. On the other hand,
drug repurposing is a process to find the new existing
drug for a new medical indication. Since Crotalus adamanteus LAAO has no crystal structure in the
protein data bank, first, its 3D structure was constructed by homology modeling using 1REO as the template and then modeled structure was evaluated by several algorithms. We screened the FDA-approved drugs by structure-based virtual screening, molecular dynamics (MD) simulation, and Molecular Mechanics Poisson Boltzmann Surface Area (MM/
PBSA) to identify new inhibitors for the
snake venom LAAO. Interestingly, docking results revealed that half of the hits belong to the
propionic acid derivatives drugs. In addition, MD simulation was performed to assess the interaction profile of the docked
protein-hits complexes. Meanwhile, Arg88, Gln112, Lys345, Trp356 form consistent hydrogen bond interactions with
Dexketoprofen,
Flurbiprofen,
Ketoprofen,
Morphine, and
Citric acid during simulation. According to the results, each of the four compounds can be an appropriate inhibitor of LAAO and since our study was based on
drug repurposing could be evaluated in phase II clinical trials.