Novel Inhibition of HIV-1 Infection Using Helix Grafted Proteins
At A Glance
Researchers at Colorado State University have patented novel therapeutics for HIV‑1 that interact with gp41, an FDA approved target, using helix‑grafted scaffold proteins.
These helix-grafted scaffold proteins significantly lowered the incidence of HIV-1 infection in CD4 positive T‑cells. In addition, the helix-grafted proteins:
(1) expressed well as recombinant proteins with relative stability in human serum;
(2) were able to sufficiently bind complex biological environments; and
(3) had extended half lives compared to competitors.
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HIV/AIDS afflicts nearly 37 million people worldwide, with a high rate of mutation – strongly suggested a need for more innovative therapies. There is no cure for HIV/AIDS, but there are many drugs available to control the virus using antiretroviral therapy (ART). ART is recommended for all infected patients – and most often in a combination of three drugs from any two classes to avoid creating drug-resistant strains of HIV. Each class of drug blocks the virus in a different way. The classes include:
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs)
- Protease inhibitors (PIs)
- Entry or fusion inhibitors
- Integrase inhibitors
Entry or fusion inhibitors make up approximately 20% of the options for physician recommended therapy ‑ having only limited drugs to choose from.
Engineered helix-grafted scaffold proteins (fitting into this class) are a growing area of interest as these novel therapeutics bind with high affinity to novel targets currently untouched by available drugs on the market. And although the general concept of protein grafting is an established method for mimicking protein surfaces, the steps to generate a successful therapeutic have eluded most.
- Therapeutic target (gp41) has been validated for therapeutic use
- gp41 is essential to HIV infection – with only one other competitor binding to this specific complex
- With only two competitors in the fusion/entry class, there is truly room to capture a larger percent of the market in comparison to the other classes
- Helix-grafted scaffold proteins are human derived and fold naturally allowing them to bind with high affinity to the gp41 complex
- The helix-grafted scaffold protein is a likely canvas for further drug discover in related fields
Walker, Susanne N., et al. “GLUE That Sticks to HIV: A Helix-Grafted GLUE Protein That Selectively Binds the HIV gp41 N-Terminal Helical Region.” ChemBioChem, vol. 16, no. 2, 2014, pp. 219–222., doi:10.1002/cbic.201402531.
Tennyson, Rachel L., et al. “Helix-Grafted Pleckstrin Homology Domains Suppress HIV-1 Infection of CD4-Positive Cells.” ChemBioChem, vol. 17, no. 20, 2016, pp. 1945–1950., doi:10.1002/cbic.201600329.
Last updated: March 2020