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Mon Aug 30, 2021, 02:40 PM

Misunderstanding preliminary scientific results led to the ivermectin fiasco [View all]

Work on cultured cells (cells grown on plastic) is considered a way to get preliminary data on whether a drug might be useful for a disease.

1000's of drugs look good on cultured cells for numerous diseases: few actually work in humans for various reasons. Hydroxychloroquine worked well in cultured cells too, btw. However, human trials showed no effect for hydroxychloroquine-- turned out the cell line used was more limited than normal human lung cells in how SARS-Cov2 could bind.

Ivermectin kills invertebrate parasites by binding to invertebrate glutamate-gated chloride channels in nerve cells, hyperpolarizing the nerve cells causing paralysis and death.

Ivermectin also appears to have antiviral activity against numerous viruses possibly due to an off-target ability to block transport of proteins into the nucleus of cells by binding to importin (IMP) α/β1. At high concentrations many drugs bind to other than their original intended target.

Last year, some scientists decided to test whether it would also work against Sars-Cov2 in cell culture. Here is the paper showing that it worked against Sars-Cov2 on cultured cells: https://www.sciencedirect.com/science/article/pii/S0166354220302011 They mention that similar favorable cell culture data for dengue virus led to a human trial which showed NO efficacy. That is typical of something working in cells on a dish but not in animals or people.

But looking at their data for Covid-19 they needed >5 uM dose of ivermectin for 50% efficacy (it's off-target after all) [they need closer to 10 ÁM to be effective] and normal human dose only brings the tissue level to .0873 ÁM-- which is 60 times too little to do any good. Basically ivermectin was DOA for Covid-19 after that realization. Data on dosing from https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1889

But that didn't stop some reading news stories and even some scientists to think it might work-- there are even clinical trials exploring its use, which will almost certainly will not show efficacy based on the need for toxic doses of the drug for the treatment to even have a chance. Why? Misunderstanding the significance of preliminary scientific results.

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