Abstract
The past couple of decades have witnessed growing interest in the therapeutic potential of melittin, the main peptide constituent of honeybee venom. Given the rapid growth of in vivo studies investigating the antimicrobial efficacy of melittin and the absence of a thorough review devoted to this subject, a critical evaluation of the literature has become both necessary and opportune. This review commences with a brief overview of the structural characteristics and biological properties of melittin, followed by an evaluation of the in vivo evidence supporting its antibacterial, antifungal, antiprotozoal, and antiviral activities. The limitations of the available studies are also considered, and future research priorities are identified to guide the continued development and clinical translation of this multifunctional peptide. Evidence indicates that melittin can reduce microbial burdens in selected experimental infection models and modulate inflammatory responses. However, the magnitude and nature of these effects vary according to the pathogen, infection model, host context, administration route, dose, and formulation. The continued development of melittin as a therapeutic candidate will require a multidisciplinary strategy. Further efforts should be made to develop biocompatible delivery platforms, including inorganic nanomaterials, polymeric carriers, lipid-based systems, and hydrogels. Additionally, combination therapies with conventional antimicrobial agents or other antimicrobial peptides should be explored. Overall, melittin represents a promising anti-infective candidate, although further studies are required to define its therapeutic window, pharmacokinetic and biodistribution profiles, long-term safety, immunogenicity, and appropriate delivery strategies.