Computational Applications: Beauvericin from a Mycotoxin into a Humanized Drug

Abstract

Drug discovery was initially attributed to coincidence or experimental research. Historically, the traditional approaches were complex, lengthy, and expensive, entailing costly random screening of synthesized compounds or natural products coupled with in vivo validation largely depending on the availability of appropriate animal models. Currently, in silico modeling has become a vital tool for drug discovery and repurposing. Molecular docking and dynamic simulations are being used to find the best match between a ligand and a molecule, an approach that could help predict the biomolecular interactions between the drug and the target host. Beauvericin (BEA) is an emerging mycotoxin produced by the entomopathogenic fungus Beauveria bassiana, being originally studied for its potential use as a pesticide. BEA is now considered a molecule of interest for its possible use in diverse biotechnological applications in the pharmaceutical industry and medicine. In this manuscript, we provide an overview of the repurposing of BEA as a potential therapeutic agent for multiple diseases. Furthermore, considerable emphasis is given to the fundamental role of in silico techniques to (i) further investigate the activity spectrum of BEA, a secondary metabolite, and (ii) elucidate its mode of action.

Keywords: beauvericin; computer-aided drug discovery; mycotoxin; natural compounds; repurposing.

Figure 1

Secondary structure of BEA, a cyclic hexadepsipeptide.

Figure 2

Molecular docking of beauvericin (BEA) with SARS-CoV-2 viral proteins. 3D surface representations of proteins in Blue and BEA is shown in red as well as in 2D diagrams. (A) SARS-CoV-2 spike protein. (B) Protease: orthosteric site. (C) Protease: allosteric pocket.

Figure 3

Schematic diagram of Bioavailability Radar for Drug likeness of BEA (lipophilicity: XLOGP3 between −0.7 and +5.0, size: MW between 150 and 500 g/mol, polarity: TPSA between 20 and 130 A2, solubility: log S no higher than 6, saturation: fraction of carbons in the sp3 hybridization not less than 0.25, and flexibility: no more than 9 rotatable bonds).

Figure 4

Schematic representation of perceptive evaluation of passive gastrointestinal absorption and Bbain penetration with BEA in the WLOGP-versus-TPSA using BOILED-Egg. The white region is for high probability of passive absorption by the gastrointestinal tract, and the yellow region (yolk) is for high probability of brain penetration. Yolk and white areas are not mutually exclusive. In addition, the points are colored in blue if predicted as actively effluxed by P-gp (PGP+) and in red if predicted as non-substrate of P-gp (PGP−).