Nanoparticles loaded with bee venom kill HIV

Anti-HIV nanoparticles

Nanoparticles (purple) carrying melittin (green) fuse with HIV (small circles with spiked outer ring), destroying the virus’s protective envelope. Molecular bumpers (small red ovals) prevent the nanoparticles from harming the body’s normal cells, which are much larger in size.
Credit: Joshua L. Hood, MD, PHD.

Nanoparticles carrying a toxin found in bee venom can destroy human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS.

“Our hope is that in places where HIV is running rampant, people could use this gel as a preventive measure to stop the initial infection,” says Joshua L. Hood, MD, PhD, a research instructor in medicine.

The study appears in the current issue of Antiviral Therapy.

Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV, and other viruses. Large amounts of free melittin can cause a lot of damage. Indeed, in addition to anti-viral therapy, the paper’s senior author, Samuel A. Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences, has shown melittin-loaded nanoparticles to be effective in killing tumor cells.

The new study shows that melittin loaded onto these nanoparticles does not harm normal cells. That’s because Hood added protective bumpers to the nanoparticle surface. When the nanoparticles come into contact with normal cells, which are much larger in size, the particles simply bounce off. HIV, on the other hand, is even smaller than the nanoparticle, so HIV fits between the bumpers and makes contact with the surface of the nanoparticle, where the bee toxin awaits.

“Melittin on the nanoparticles fuses with the viral envelope,” Hood says. “The melittin forms little pore-like attack complexes and ruptures the envelope, stripping it off the virus.”

According to Hood, an advantage of this approach is that the nanoparticle attacks an essential part of the virus’ structure. In contrast, most anti-HIV drugs inhibit the virus’s ability to replicate. But this anti-replication strategy does nothing to stop initial infection, and some strains of the virus have found ways around these drugs and reproduce anyway.

“We are attacking an inherent physical property of HIV,” Hood says. “Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.”

Beyond prevention in the form of a vaginal gel, Hood also sees potential for using nanoparticles with melittin as therapy for existing HIV infections, especially those that are drug-resistant. The nanoparticles could be injected intravenously and, in theory, would be able to clear HIV from the blood stream.

“The basic particle that we are using in these experiments was developed many years ago as an artificial blood product,” Hood says. “It didn’t work very well for delivering oxygen, but it circulates safely in the body and gives us a nice platform that we can adapt to fight different kinds of infections.”

Since melittin attacks double-layered membranes indiscriminately, this concept is not limited to HIV. Many viruses, including hepatitis B and C, rely on the same kind of protective envelope and would be vulnerable to melittin-loaded nanoparticles.

While this particular paper does not address contraception, Hood says the gel easily could be adapted to target sperm as well as HIV. But in some cases people may only want the HIV protection.

“We also are looking at this for couples where only one of the partners has HIV, and they want to have a baby,” Hood says. “These particles by themselves are actually very safe for sperm, for the same reason they are safe for vaginal cells.”

While this work was done in cells in a laboratory environment, Hood and his colleagues say the nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

(news.wustl.edu. March 7, 2013)

 

Reference

Hood JL, Jallouck AP, Campbell N, Ratner L, Wickline SA. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antiviral Therapy 2013; 19: 95-103.

 

Seeking HIV Treatment Clues in the Neem Tree

Preliminary data hint at how extracts from the tree, abundant in tropical and subtropical areas, may stop the virus from multiplying 

Tall, with dark-green pointy leaves, the neem tree of India is known as the “village pharmacy.” As a child growing up in metropolitan New Delhi, Sonia Arora recalls on visits to rural areas seeing villagers using neem bark to clean their teeth. Arora’s childhood memories have developed into a scientific fascination with natural products and their power to cure illnesses. Now an assistant professor at Kean University in New Jersey, Arora is delving into understanding the curative properties of the neem tree in fighting the virus that causes AIDS. Sonia Arora presented her data at a poster session Sunday, April 22, at the Experimental Biology 2012 meeting in San Diego. Her preliminary results seem to indicate that there are compounds in neem extracts that target a protein essential for HIV to replicate. If further studies support her findings, Arora’s work may give clinicians and drug developers a new HIV-AIDS therapy to pursue. Extracts from neem leaves, bark and flowers are used throughout the Indian subcontinent to fight against pathogenic bacteria and fungi. “The farther you go into the villages of India, the more uses of neem you see,” says Arora. Tree branches are used instead of toothpaste and toothbrushes to keep teeth and gums healthy, and neem extracts are used to control the spread of malaria. Practitioners of Ayurvedic medicine, a form of traditional Indian alternative medicine, even prescribe neem extracts, in combination with other herbs, to treat cardiovascular diseases and control diabetes. The neem tree, whose species name is Azadirachta indica and which belongs to the mahogany family, also grows in east Africa. Arora’s scientific training gave her expertise in the cellular biology of cancer, pharmacology, bioinformatics and structural biology. When she established her laboratory with a new research direction at Kean University in 2008, Arora decided to combine her knowledge with her long-time fascination with natural products. The neem tree beckoned. Arora dived into the scientific literature to see what was known about neem extracts. During the course of her reading, Arora stumbled across two reports that showed that when HIV-AIDS patients in Nigeria and India were given neem extracts, the amount of HIV particles in their blood dropped. Intrigued, Arora decided to see if she could figure out what was in the neem extract that seemed to fight off the virus. She turned to bioinformatics and structural biology to see what insights could be gleaned from making computer models of HIV proteins with compounds known to be in neem extracts. From the literature, she and her students found 20 compounds present in various types of neem extracts. When they modeled these compounds against the proteins critical for the HIV life-cycle, Arora and her team discovered that most of the neem compounds attacked the HIV protease, a protein essential for making new copies of the virus. Arora’s group is now working on test-tube experiments to see if the computer models hold up with actual samples. If her work bears out, Arora is hopeful that the neem tree will give a cheaper and more accessible way to fight the HIV-AIDS epidemic in developing countries, where current therapies are priced at levels out of reach of many people. “And, of course,” she notes, “there is the potential of discovering new drugs based on the molecules present in neem.”