I find this interplay fascinating, the product of an evolutionary war with viruses trying to find ways to multiply and the body dealing with it. SA is a binding target so RBC, platelets and leukocytes express SA as decoys to keep viruses away from target cells. The beta coronavirus like the common cold have HE which collapses the hemagglutinated sheet, acting against its own mechanisms to increase its infectivity and reducing lethality in the host.

Incidentally this is relevant to the MOA theorised by Nitazoxanide, another anti-parasitic molecule. One proposed mechanism is Nitazoxanide causes viral hemagglutinin protein to be defective upon formation of the virus, so that SARS-CoV-2 viruses will have less ability to cause clotting. The Whiteboard Doctor did a video on this and some studies showing early promise of efficacy.

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Dr. Scheim posted this article (which he authored) with an inappropriate title. Here is what he wrote with his post.

I've been asked to create a posting on my recently released preprint, which briefly reviews 8 clinical studies on ivermectin (IVM) in its concluding section. The record of clinical efficacy of IVM for COVID-19 is striking, and it seems that we haven't begun to ride the dose-response curve to best results at highest, safe dosages. It is important to present a credible scientific foundation for how IVM counteracts SARS-CoV-2--this preprint provides that, citing 6 different studies that conclude that IVM blocks the viral spike protein. It's important to know that this binding occurs not just to ACE2, which is the site of viral fusion and replication, but to sialic acid receptors, the points of initial attachment, the role of which is critical.

One can only command the Caly-Wagstaff team for initially exploring activity of IVM against SARS-CoV-2, and their work attracted the interest of many others. Science advances as hypothesis are put forth and inspire new thinking, even when they prove to be utterly bogus, as is the case for the Caly-Wagstaff work (more than 1, 000 times physiological tissue concentrations, does not apply to RNA viruses). It is important for anyone trying to move forward the study and deployment of IVM for COVID-19 to take the time to look at the underlying science.

This preprint, http://ssrn. com/abstract=3706347, is entitled: From cold to killer: How SARS-CoV-2 evolved without hemagglutinin esterase to agglutinate, then clot blood cells in pulmonary and systemic microvasculature. Among the points of key interest:

· Viruses of many strains attach to RBCs, the basis of the classic hemagglutination assay refined by Jonas Salk in the 1940s.

· SARS-COV-2, in particular, agglutinates with RBCs in vitro, as manifested clinically in microvascular occlusion—as seen in tissues from COVID-19 patients using ultramicroscopy and immunochemistry.

· Such agglutination and occlusion in pulmonary capillaries cause oxygen deficits, while alveoli often remain intact and lung mechanics are normal.

· Sialic acid and CD147 receptors are the points of initial attachment by SARS-CoV-2 to host and blood cells, prior to fusion and replication via ACE2, as definitively established in many studies.

· Ivermectin (IVM), a macrocyclic lactone of Nobel prize-honored distinction, limits hemagglutination by competitive SARS-COV-2 spike protein binding. IVM has demonstrated major clinical benefits for COVID-19 in several studies, with potential for more dramatic gains with tenfold, safe dose escalation.

My email address is listed in the preprint, and feel free to contact me if you'd like to discuss this, or to alert me if you've posted something here. - David

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