Researchers at the University of Utah have discovered a new class of compounds that strongly bind to the sugar coating of the AIDS virus, making possible a new ointment that could prevent HIV from infecting host cells.
Decades have coasted past scientists who have been working to fight against HIV to prevent AIDS, or acquired immune deficiency syndrome. Despite years of research, only one microbicide has been successful against the prevention of HIV transmission. To prevent sexual transmission of HIV, production of microbicides have been gearing towards gel or cream products that can be vaginally applied by women.
Although there has been increasingly common knowledge of HIV prevention by condoms, reduced amount of sexual partners and diagnosis, the HIV virus is spreading at a drastic rate, especially in the developing countries. Unfortunately, the most feasible methods are out of reach for women in the resource poor settings. As an alternative to condoms, microbicides offer a very feasible method of primary prevention.
Microbicides can work in different ways, depending on their target. Some provide physical protection that keep HIV and other pathogens from entering the system, while others boost the vaginal defense mechanisms, such as maintenance of the acidic environment. Many pathogens cannot function in such conditions.
The replication of HIV in a host is a multi-stage process, each of which is crucial for the success of its survival. Conversely, targeting each step is crucial for the success effective drugs.
In order to infect a cell, HIV first binds to a host cell within the immune system, such as the CD4+ T-lymphocyte, a type of white blood cell. It then inserts its hydrophobic terminus into the cell membrane, pulling the viral capsid into the host cell. The capsid, a protein coating surrounding the virus, contains 2 RNA strands and the enzymes integrase, protease and reverse transcriptase.
Reverse transcriptase begins the reverse transcription, creating its own double-stranded DNA from the RNA single strands. Integrase cleaves the DNA to create two sticky ends, and then facilitates the viral gene to integrate into the host DNA. When the host DNA is activated, transcription and translation occurs - this expresses the viral gene and produces some of the proteins encoded by the viral DNA.
Then the protease cleaves longer proteins into smaller core proteins, which is crucial to create an infectious virus. Two viral RNA strands and replication enzymes, transcribed from the viral DNA, gather while core proteins surround them, creating a virus that can diffuse out of the host cell and infect other cells.
The compound for the potentially new microbicide, discovered by researchers at University of Utah, does not attack the core machinery of replication, but blocks the first step: the binding of the HIV to host cells. Lectin is a natural molecule derived from plants. However, due to its excessive cost to purify, the researchers synthesized lectin based on a compound called benzoboroxole, or BzB, a compound that sticks to the sugar-coating found on the HIV envelope.
Initially, BzB-based lectins bonded too weakly with the sugar molecules on HIV to be deemed useful as a drug compound. However, they increased bonding potential by designing a polymer, a larger molecule made up of a chain of the same molecule, of lectin. This substantially amplified the binding power to the AIDS virus, reducing viral activity.
The researchers also found that these lectins fought against a broad spectrum of HIV strains, indicating a defensive mechanism that targets the sugar molecule of HIV, regardless of variations in viral envelopes. They also tested lectins in the presence of fructose, a sugar present in semen, which could compromise lectin activity by acting as an alternative binding site. However, test results have indicated no change in activity.
According to the research team, the BzB lectin protein may fit the criteria for an ideal anti-HIV microbicide and could be a very ideal method of HIV prevention for women around the world.
