Structure-based virtual screening to predict Loxosceles spider venom natural inhibitors

Abstract

Objective: Loxosceles spider bite accidents are rising in wide areas of the world which necessitates the exploration of natural inhibitors to inhibit the most significant enzymes, namely sphingomyelinase D (Smase D) and hyaluronidase. Methods: Virtual screening using traditional Chinese medicine (TCM) against Smase D (PDB ID: 2F9R) and hyaluronidase was performed by the DrugRep server. Absorption, distribution, metabolism, and excretion (ADME) parameters were predicted via the same server. In addition, molecular dynamics (MD) simulation was conducted using CABS-flex 2.0 tool to prioritize the best potential natural inhibitors. Results: Tiliroside and Digitoxin were the best natural inhibitors from TCM to Smase D and hyaluronidase in terms of molecular docking and ADME parameters, while Digitoxin and β-carotene were the most potent inhibitors against hyaluronidase. MD simulations demonstrated the stability of the docked complexes. Conclusion: In-silico inhibition of Loxosceles spidervenom enzymes through TCM was demonstrated, which deserves wet-lab experimentation.

Keywords

• Loxoscelesspider
• Sphingomyelinase D (Smase D)
• Traditional Chinese medicine (TCM)
• Molecular docking
• Molecular dynamics (MD) simulations
• Absorption