Physicochemical, medicinal chemistry, and ADMET characteristics of bee antimicrobial peptides as natural bio-preservatives to extend food shelf life: a roadmap for food safety regulation.

Abstract

Antimicrobial peptides (AMPs) are gaining popularity as potential substitutes for conventional antibiotics and bio-preservatives in response to an increase in antimicrobial resistance cases. However, their poor pharmacokinetic profiles limit their applicability. This study using ADMETlab, OECD QSAR toolbox, and VEGA HUB virtual environments profiled 82 peptide sequences of seven bee antimicrobial peptides (BAMPs: abaecin, apamin, apisimin, apidaecin, defensin, hymenoptaecin, and melittin) using 81 descriptors combining physicochemical, medicinal chemistry, ADMET, and toxicophore criteria. BAMPs adhere to key drug-like physicochemical features and drug-ability regulations set forth by pharmaceutical giants, including Lipinski, Pfizer, and GlaxoSmithKline. BAMPs have been predicted to demonstrate favorable cell permeability, high water solubility, oral bioavailability, no blood-brain barrier penetration, oral and intestinal absorption, excretion, and a high therapeutic index. They function as non-substrates of p-glycoprotein and do not alter the pharmacokinetic effects of P-gp substrates. None of BAMPs were found to inhibit cytochrome P450 enzymes, indicating their potential to promote drug clearance and metabolism. BAMPs are safe from adverse reactions, free of respiratory toxicity, hERG blockers, hepatotoxicity, sensitizers, carcinogens, and mutagens. They are non-corrosive, non-irritating to the eyes, non-bioaccumulative, non-ecotoxic, antibacterial, antifungal, and antiviral, low toxic with no toxicophore or PAINS alerts recorded. They are non-toxic to various receptors, including gonadal and stress receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. Seven BAMPs have been tested for their drug-like properties, supporting their potential as potential leads for the pharmaceutical and food industries as antimicrobial agents and bio-preservatives. Future studies should optimize bee peptide expression in biological systems.