The medicinal use of bee products, known as apitherapy, has existed for thousands of years. In Ancient Greece, Egypt, and China dating back 3000-5000 years, honey was applied to cuts and sores to prevent infection, and prescribed for coughs and illness (Khalil et al. 2021). Documented by Greek and Roman physicians Hippocrates and Galen who referenced the use of apitherapy for treating the sick (Kim 2013). Much later, in the 1800’s, research was published on the use of bee stings to treat rheumatism, reduce inflammation, and treat skin cancer (Kim 2013). The past couple decades has revealed the extent of uses for bee products, markedly, the use of honey bee venom in the treatment of HIV.
Human immunodeficiency virus (HIV) targets CDT4 white blood cells, attacking the immune system and making it vulnerable to disease and infection (Fauci et al. 1996). The virus replicates chronically in the body and can be held at a low level with drugs on the market (Fauci et al. 1996). Untreated, it leads to acquired immunodeficiency syndrome (AIDS) which can be fatal (Fauci et al. 1996). Several drugs exist to manage and extend life expectancy for individuals with HIV, including nucleotide analogue reverse-transcriptase inhibitors, protease inhibitors, and fusion inhibitors. However, there is yet to be a cure for the disease (Memariani et al. 2020). Additionally, current treatment options can lead to virus mutational resistance in as little as 2 weeks (Hood et al. 2013).
European honeybee (Apis mellifera) venom contains metabolites and peptides, one of which is melittin which composes 40-60% the dry weight of bee venom (Sleman et al. 2026; Yaacoub et al. 2023; Wehbe et al. 2019). It shows antimicrobial property against gram positive and gram negative bacteria, and antiviral activity against herpes simplex virus 1 and 2, influenza, HIV, SARS CoV-2, as well as anti-cancer abilities (Wehbe et al. 2019; El-Seedi et al. 2020; Zhang et al. 2024)
Melattin is an amphipathic peptide, meaning it possesses both hydrophobic and hydrophilic properties, composed of 26 amino acids shaped into two connected alpha helixes (Memariani et al. 2020). It is a membranolytic agent, meaning it causes cell lysis by triggering pore formation on the cell membrane which disrupts cell function in several viruses, including HIV (Memariani et al. 2020). Using the maximum free melittin dose which is not harmful to healthy cells (2 µM/L), the ability of the CCR5 strain of HIV to infect cells was reduced to less than 10% and to 0% using >6 µM/L dose (Hood et al. 2013). To avoid harming healthy cells, melittin was loaded onto blank nanoparticles which have size selectivity for HIV infected cells which are smaller than healthy cells (Figure 1).
Using nanoparticles, in vitro human vaginal epithelial cell viability was not decreased at any melittin concentration tested, including ones found harmful using free melittin (Hood et al. 2013). Additionally, melittin physically targets the virus’s double membrane, making HIV resistance unlikely—highly relevant HIV treatment given the potential for virus mutational resistance with current market drugs (Hood et al. 2013).
Though apitherapy has been used for thousands of years, its credibility in today’s scientific landscape is relatively young and the medicinal uses of honey bee venom exemplifies the importance of studying science of the past.
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