@Covid19Crusher @jpkiekens @Ian56789 @gummibear737

How to Crush COVID-19 with Early Treatment

SARS-CoV-2 gets into cells either via endosomes, or directly thru the plasma membrane. This requires fusion of the viral lipid membrane with the endosomal or plasma membrane.

But this merger is blocked by the viral spike protein, which protrudes from the viral membrane and is needed for binding to cells via ACE2. This protein must be proteolytically cleaved before membrane fusion can occur.

In endosomes, this proteolytic activity is provided by cathepsin L. This enzyme requires acidity for activity. Both HCQ and AZM accumulate in endosomes and alkalinize them - thereby inhibiting cathepsin L and preventing SARS-CoV-2 from entering cells via the endosomal route.

But that's not good enough, because the plasma membrane route is still open. A plasma membrane protease, TMPRSS2, is able to cleave the viral spike protein. This enables membrane fusion, so that the viral nucleoproteins can enter the cell and initiate replication.

So evidently what we also need is a safe TMPRSS2 inhibitor. That's where bromhexine comes in. In vitro studies show that this safe drug can inhibit TMPRSS2 - and thus should impede viral entry through the plasma membrane.

The problem with this idea is that we didn't know what dose of bromhexine would be required to achieve this clinically. But this new Iranian study suggests that the standard clinical dosage for bromhexine - 8-16 mg, 3 X daily - should suffice.

https://bi.tbzmed.ac.ir/Files/Inpress/bi-23240.pdf

So use HCQ/AZM to block endosomal route; use bromhexine to block plasma membrane route. Virus can't get into cells. Immune mechanisms eliminate already-infected cells. End of infection. So simple that anyone can understand it except for those paid NOT to understand.

So I suggest this simple regimen for early Rx:

Bromhexine – 8-16 mg 3 times daily
Hydroxychloroquine – 1st day 400 mg twice; subsequent days 200 mg twice daily
Azithromycin 500 mg once daily

By physician prescription ONLY; appropriate contraindications must be observed.

Key citations:
https://link.springer.com/article/10.1208/s12248-020-00465-w
https://pubmed.ncbi.nlm.nih.gov/32221306/ 
https://pubmed.ncbi.nlm.nih.gov/32221306/ 
https://pubmed.ncbi.nlm.nih.gov/32458206/ 
https://bi.tbzmed.ac.ir/Files/Inpress/bi-23240.pdf

PUNCHLINE: Bromhexine is available globally as an inexpensive, safe OTC mucolytic agent. Only one problem: it's NOT available in the US and Canada, except in certain pet products. All hail to the ever-vigilant drug regulatory authorities of the US and Canada!

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