A Link Between Feline And Human Medicine Could Benefit HIV Treatment In Humans
Two scientists from the Technion–Israel Institute of Technology in Haifa, Prof. Akram Alian and Dr. Meytal Galilee, recently deciphered the structure of a protein in feline immunodeficiency virus (FIV) that also presents itself in human immunodeficiency virus (HIV).
Alian and Galilee contend that their findings could serve as the building blocks towards the formulation of new drugs to counteract the drug resistance of HIV-1. “Our discovery can assist in the development of next generation anti-HIV inhibitors that can overcome the resistance now seen in the feline virus, which, perhaps, can be accessible to therapeutically challenged HIV-1 viruses in the future,” said Galilee.
To reach these conclusions, the two researchers focused on the reverse transcriptase (RT) protein. RT is the target for the majority of anti-HIV-1 drugs. RT catalyzes the central step in the virus replication cycle converting the viral RNA genome into DNA for subsequent integration into the host genome. Alian and Galilee resolved the protein using purification and crystallization techniques in order to analyze its structure.
When asked what led them to examine reverse transcriptase from FIV, Alian responded, “Reverse transcriptase of the feline virus is particularly interesting because it is inherently resistant to all allosteric drugs targeting the HIV-1 enzyme. We anticipated that underscoring the puzzling resistance mechanisms of the feline enzyme would provide important breakthroughs in the anti-HIV field.”
Through their structural analysis of the FIV reverse transcriptase protein, the researchers discovered that it generates a “closed” pocket that could prevent reverse-transcriptase inhibitor (RTI) binding. This binding blocks the protein, so its prevention essentially renders the protein resistant to the drugs.
The research team believes their discovery will have a beneficial impact on future studies into HIV-1 drug resistance.
“Our discovery can provide researchers with a fresh template for reverse transcriptase, which is targeted by the majority of anti-AIDS drugs. This template can now be exploited for the design of next generation inhibitors,” said Alian.
The researchers reported their findings in the journal PLOS Pathogens, which you can view in its entirety by clicking here.