Many fungal diseases remain poorly addressed by public health authorities, despite posing a substantial threat to humans, animals, and plants. More worryingly, few classes of anti-fungals have been developed to combat fungal infections thus far. These medications also have certain drawbacks in terms of toxicity, spectrum of activity, and pharmacokinetic properties. Hence, there is a dire need for discovery of novel anti-fungal agents. Melittin, the main constituent in the venom of European honeybee Apis mellifera, has attracted considerable attention among researchers owing to its potential therapeutic applications. To our knowledge, there has been no review pertinent to anti-fungal properties of melittin, prompting us to synopsize the results of experimental investigations with a special emphasis upon underlying mechanisms. In this respect, melittin inhibits a broad spectrum of fungal genera including Aspergillus, Botrytis, Candida, Colletotrichum, Fusarium, Malassezia, Neurospora, Penicillium, Saccharomyces, Trichoderma, Trichophyton, and Trichosporon. Melittin hinders fungal growth by several mechanisms such as membrane permeabilization, apoptosis induction by reactive oxygen species-mediated mitochondria/caspase-dependent pathway, inhibition of (1,3)-β-D-glucan synthase, and alterations in fungal gene expression. Overall, melittin will definitely open up new avenues for various biomedical applications, from medicine to agriculture. KEYPOINTS: • Venom-derived peptides have potential for development of anti-microbial agents. • Many fungal pathogens are susceptible to melittin at micromolar concentrations. • Melittin possesses multi-target mechanism of action against fungal cells.
