Something I just posted over on stocktwits -
One of the
Something I just posted over on stocktwits -
One of the reasons leronlimab is more effective is 100% receptor occupancy, maraviroc tops out at 85%. Another may be that maraviroc as an allosteric inhibitor changes the geometry of the CCR5 receptor so that ligands can't attach. I've read the papers on conformational change with maraviroc and they're mind numbing. My suspicion with maraviroc is it doesn't always block ligands or HIV even when docked.
In early Progenic's papers they made the claim that leronlimab does not stop all activities of the CCR5 receptor. Cytodyn still goes by that today as claiming it as an immunomodulator. Last year I proposed that they may be wrong. I think leronlimab does stop all ligand binding of CCR5. All of the CCL ligands use the N terminus to bind CCR5 and leronlimab completely blocks it.
Here's how I think the immunomodulation works . Blocking of inflammatory ligands and their downstream effects. Increases in natural killer T-cells. Macrophage differentiation from M2 to M1 macrophages. Importantly the CCR1, CCR2, CCR3 and CCR4 receptors collectively bind all the ligands of CCR5.
In a regular state CCR1-4 are not widely expressed and have weaker binding then CCR5. During an inflammatory state the expression of CCR1-4 would increase to a point that the ligand response would be near that of CCR5 in a non-inflammatory state. So CCR1-4 would maintain a normal immune response and CCR5 blocking knocks down the overactive response.
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