Bee venom kills HIV cells, new study.

Scientists have recently found that a key ingredient in bee venom destroys HIV without harming other cells. The researchers loaded the toxin, called mellitin, onto nanoparticles fashioned with “bumpers” that normal, larger cells bounced off of unharmed. HIV is small enough that it fits between the bumpers and makes contact with the surface of the nanoparticles, where the bee toxin awaits. Melittin on the nanoparticle fuses with the viral envelope and ruptures it, stripping the virus’s shell.

The difference between this technique and existing anti-HIV drugs is that most drugs attempt to inhibit the virus’s ability to replicate, which the virus is able to evolve to evade. These drugs also don’t arrest the initial infection. But melittin attacks the virus’s inherent structure. There’s theoretically no way to develop adaptive evasion responses to that.

The antiviral therapy has implications for areas rampant with HIV, to be used by women in a vaginal preventative gel that prevents the initial infection. Treatments could also be developed for drug-resistant HIV infections, to be delivered intravenously and potentially clear the blood of the infection. There is also the possibility for this treatment being useful for couples in which one member is HIV-positive but who want to have a baby together.

The nanoparticle itself was developed years ago for an artificial blood experiment, but it was lousy at carrying oxygen. It’s proving its worth now as a promising drug-delivery system instead: the particle can be loaded to target all kinds of infections.

Mellitin attacks double-layered membranes, like the kind many viruses use, indiscriminately, which also means that other viruses like Hepatitis B and C, which rely on a protective envelope to evade the body’s immune system, could be slayed by this potent little toxin. Researchers say the nanoparticles are easy enough to make that they can be reproduced for clinical trials soon.

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Abstract
BACKGROUND:
We investigated whether cytolytic melittin peptides could inhibit HIV-1 infectivity when carried in a nanoparticle construct that might be used as a topical vaginal virucide. Free melittin and melittin-loaded nanoparticles were prepared and compared for cytotoxicity and their ability to inhibit infectivity by CXCR4 and CCR5 tropic HIV-1 strains.

METHODS:
TZM-bl reporter cells expressing luciferase under the control of the HIV-1 promoter were incubated with HIV-1 NLHX (CXCR4) or HIV-1 NLYU2 (CCR5) viral strains and different doses of soluble CD4 (positive control) or free melittin to determine infectivity and viability. Melittin-loaded nanoparticles were formulated and different doses tested against VK2 vaginal epithelial cells to determine cell viability. Based on VK2 viability, melittin nanoparticles were tested for prevention of CXCR4 and CCR5 tropic HIV-1 infectivity and viability of TZM-bl reporter cells. Low-speed centrifugation was used to compare the ability of blank non-melittin nanoparticles and melittin nanoparticles to capture CCR5 tropic HIV-1.

RESULTS:
As expected, the soluble CD4 positive control inhibited CXCR4 (50% inhibitory concentration [IC₅₀] 3.7 μg/ml) and CCR5 (IC₅₀ 0.03 μg/ml) tropic HIV-1 infectivity. Free melittin doses <2 μM were not cytotoxic and were highly effective in reducing HIV-1 infectivity for both CXCR4 and CCR5 strains in TZM-bl reporter cells, while VK2 vaginal cell viability was adversely affected at all free melittin doses tested. However, VK2 cell viability was not affected at any dose of melittin-loaded nanoparticles. Melittin nanoparticles safely and significantly decreased CXCR4 (IC₅₀ 2.4 μM and IC₉₀ 6.9 μM) and CCR5 (IC₅₀ 3.6 μM and IC₉₀ 11.4 μM) strain infectivity of TZM-bl reporter cells. Furthermore, melittin nanoparticles captured more HIV-1 than blank nanoparticles.

CONCLUSIONS:
These data illustrate the first proof-of-concept for therapeutic and safe nanoparticle-mediated inhibition of HIV-1 infectivity. Future investigations appear warranted to explore the antiviral prophylactic potential of melittin nanoparticles to capture, disrupt and prevent initial infection with HIV-1 or potentially other enveloped viruses.

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http://blogs.discovermagazine.com/visualscience/2013/03/17/chemical-in-bee-venom-kills-hiv/#.UZU080opnFw
http://www.ncbi.nlm.nih.gov/pubmed/22954649