Human immunodeficiency virus (HIV), the virus that causes the devastating acquired immunodeficiency syndrome (AIDS) currently infects over 35 million people worldwide. Since the first reported cases in 1981, more than 25 million people have died of AIDS. In the United States alone, over 50,000 people are newly infected each year. While some current anti-retroviral treatments can slow the progression of AIDS, there is no cure. Therefore, methods to prevent infection before it starts are the key to fighting the spread of HIV. An effective vaccine has yet to be developed, so other prevention techniques like anti-viral microbicides are highly-desirable. Current anti-retroviral medications are made of synthetic materials, making them expensive. Use of these drugs is thus cost-prohibitive for many patients with AIDS, most of whom live in low- and middle-income countries. As an added disadvantage of current anti-HIV drugs, the virus can mutate and become resistant to them. A modified plant molecule that evades resistance may provide an inexpensive answer to the limitations of current methods for HIV prevention.
An alteration of a single amino acid in banana lectin to avoid mitogenicity but maintain anti-viral effects
In 2010, biologists discovered that a chemical derived from bananas called banana lectin had anti-HIV properties. Banana lectin binds to mannose, a type of sugar found in many plants. The scientists found that by binding to a sugar-rich protein called gp120 on the surface of HIV, banana lectin halts the series of events by which HIV causes infection. In other words, banana lectin can stop HIV infection in its tracks by blocking the virus before it has a chance to integrate into human cells. In addition, banana lectin is as potent as two currently-used anti-HIV drugs, T-20 and maraviroc. Researchers were unable to immediately advance the lectin towards preclinical trials, though. Despite its obvious promise as a potent anti-viral treatment, natural banana lectin has the drawback of activating cell division, or mitosis, which can be a safety concern. The new goal is thus to engineer a version of banana lectin that maintains its anti-viral features but does not cause harmful mitogenicity. Recent biochemical experiments have taken the first step in this process by identifying the molecular basis for these mitogenic properties. When a specific amino acid in the sequence for banana lectin is replaced by a different amino acid, it changes the conformational flexibility of the lectin’s protein structure. This single change eliminates the mitogenicity of the banana lectin. By taking advantage of this single amino acid, future recombinant versions of banana lectin can be developed that maintain their anti-viral effect but forgo mitogenicity.
Because banana lectins appear in nature, they could be less expensive to produce than the synthetic anti-HIV treatments currently in use. In addition, lectins have the added advantage of making it more difficult for the virus to mutate and become resistant, a problem that appears with many anti-HIV drugs. If present strategies to develop banana lectin in this way prove to be effective, similar techniques can be used to identify the structural bases for mitogenicity in related lectins with similar folding mechanisms, such as those in the jacalin and artocarpin families.
- Prevention of HIV infection
- Potential development as prevention and/or treatment of other viruses like hepatitis C virus (HCV), severe acute respiratory syndrome (SARS), influenza, and Middle East respiratory syndrome (MERS)
- Avoids unwanted cell division (mitogenicity)
- Production less expensive than current synthetic drugs
- Mitigates drug resistance by hindering viral mutations