Melittin

Melittin makes up roughly 40-60% of the dry weight of Apis mellifera venom. It is a bent amphipathic helix that binds membrane surfaces at low concentration and, above a threshold, oligomerises into toroidal pores that permeabilise the bilayer. It also activates phospholipase A2 — which is itself a major venom component — amplifying membrane damage and inflammatory lipid mediator production. Its antimicrobial spectrum is broad and includes MRSA and mycobacteria; it disrupts the lipid envelope of HIV, influenza and herpesviruses; and it kills tumour cells in culture at low micromolar concentrations. The problem is that none of this is selective. Free melittin is strongly haemolytic and causes profound local pain, so essentially all serious drug development has focused on delivery vehicles that hide it until it reaches the target — nanoparticle 'nanobees', tumour-targeted conjugates and hybrid peptides with the lytic face attenuated. None has reached late-stage clinical use.

Targets: Lipid bilayers, Phospholipase A2, Viral envelopes, Erythrocyte membranes

• · Typical in vitro antimicrobial and cytotoxic concentrations are in the low micromolar range. There is no validated human dosing for isolated melittin by any route, and anyone quoting one is guessing.
• · Practised mainly in Korea and China using whole bee venom, typically diluted 1:10,000 to 1:1,000 and escalated slowly from very small volumes. Melittin content is not standardised between preparations. Fatal anaphylaxis from this practice is documented in the literature — this is not a benign traditional remedy.
• · Cosmetic creams contain purified venom at fractions of a percent. Effects on skin are largely irritant-mediated and the antimicrobial claims are not supported by controlled evidence.

Work out your exact syringe units →

• very commonSevere local pain, swelling and erythema— This is the sting reaction. It is the expected consequence of injecting a cytolytic peptide into tissue.
• commonHaemolysis— Melittin lyses erythrocytes at concentrations barely above its antimicrobial range. This narrow therapeutic window is the single reason it has never become a systemic drug.
• uncommonAnaphylaxis— Bee venom is one of the classic causes of fatal anaphylaxis. Deaths from bee venom acupuncture are documented in the medical literature.
• uncommonSerum sickness-like delayed reactions— Fever, arthralgia and rash days after exposure.
• rareRhabdomyolysis and acute kidney injury— Reported after massive envenomation or aggressive apitherapy.

• Any known bee or wasp venom allergy — absolute.
• Any systemic or intravenous administration of free melittin; the haemolytic dose overlaps the therapeutic dose.
• Mastocytosis or a history of anaphylaxis to any allergen.
• Use without immediate access to adrenaline and resuscitation equipment.
• Pregnancy, given the inflammatory mediator release and lack of any safety data.

• conflictbeta-blockers — Beta-blockade makes anaphylaxis harder to treat with adrenaline — a serious issue for anyone receiving venom-based therapy.
• cautionACE inhibitors — Associated with more severe systemic reactions to hymenoptera venom.
• cautionantihistamines — Pre-medication may blunt early warning symptoms of a developing anaphylactic reaction without preventing it.

• · Direct supervision for at least 30 minutes after any venom exposure, with adrenaline immediately available.
• · Haemoglobin, LDH and haptoglobin if haemolysis is suspected.
• · Creatine kinase and renal function after significant envenomation.
• · Tryptase if anaphylaxis is suspected.

Not a drug in any jurisdiction. Sold as a research chemical and as an ingredient in cosmetics and traditional apitherapy preparations, which are essentially unregulated.

• Raghuraman & Chattopadhyay, melittin as a model membrane-active peptide (review)
• Memariani et al., melittin as an antimicrobial and antiviral agent (review)
• Case reports of fatal anaphylaxis following bee venom acupuncture (other)

The principal cytolytic component of honeybee venom - a 26-residue amphipathic peptide that inserts into membranes and forms toroidal pores. It is genuinely potent against bacteria, fungi and tumour cells in vitro, and equally potent against erythrocytes and every other human cell, which is the entire obstacle.

Selectivity, entirely. The in vitro anticancer literature is extensive and is routinely quoted without the accompanying fact that the same concentrations lyse red cells. Bee venom therapy also carries a real anaphylaxis risk, and deaths have been reported.

• Phospholipid bilayers, non-selectively — Amphipathic membrane insertion

  Toroidal pore formation and lysis, without discriminating host from pathogen

Immediate lysis on contact at active concentrations.

• ?Nanoparticle and conjugate delivery approaches aim to solve the selectivity problem; none has reached clinical use.