@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.

bi.tbzmed.ac.ir/Files/Inpress/…
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.
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!

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Mark F. McCarty

Mark F. McCarty Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @markfmccarty

Sep 3, 2020
@Covid19Crusher @jpkiekens @niro60487270 @Ian56789

Here's a paper which may be a Rosetta Stone for understanding the favorable impact of good vit D status in COVID19:

pubmed.ncbi.nlm.nih.gov/22301548/
In human monocytes expressing the 1alpha-hydroxylase activity needed to convert 25OHD to the active hormone calcitriol, physiological levels of 25OHD induce expression of MAPK phosphatase-1 (MPK1), which functions to deactivate p38 MAPK.
p38 is typically activated during inflammation, and, via up-regulated activity of AP-1 and NF-kappaB transcription factors, promotes transcription of a wide range of pro-inflammatory cytokines, including many (e.g. IL-6, TNF-alpha) that are key mediators of COVID-19 inflammation.
Read 10 tweets
Jul 29, 2020
@filipe_rafaeli

The key proposition on the table is this: HCQ + AZM +/- Zn, administered just as soon as symptoms arise, greatly reduces need for subsequent hospitalization and risk of death.
I have aggregated all reported large case series I can find evaluating this protocol (including those in Table 1 of Dr. Risch's new letter: pubmed.ncbi.nlm.nih.gov/32685966/) - many focusing on high-risk patients.
I calculate a case-fatality rate of about 0.4% - one-tenth that of Germany (4%). The latter is a good comparator, since Germany tests extensively (lowering the CFR), and has first-rate supportive care - but HCQ use is minimal. Case-series from physicians on 3 continents.
Read 8 tweets
Jun 29, 2020
@Covid19Crusher

SARS-CoV-2 virions attach to the ACE2 membrane protein, then are taken into cells engulfed in endosomes. In order to break into the cytoplasm – where the virus can replicate – the lipid envelope of the virions must fuse with the endosomal membrane.
Cleavage of the viral spike protein by the enzyme cathepsin L is required for this fusion.

pubmed.ncbi.nlm.nih.gov/32221306/ pubmed.ncbi.nlm.nih.gov/32470470/
Cathepsin L’s activity is pH dependent; it’s optimal at the acidic pH that normally prevails in endosomes, but is inhibited at neutral or alkaline pH. Hence, endosomal alkalization can slow the ability of SARS-CoV-2 to spread from cell to cell.

pubmed.ncbi.nlm.nih.gov/3382672/
Read 17 tweets
Jun 21, 2020
#LancetGate @jpkiekens @niro60487270

The NIH has just shut down its multicenter RCT of HCQ/AZM in early stage COVID-19 outpatients, due to anemic enrollment. After over a month, only 20 subjects had enrolled, whereas the target enrollment was 2,000.

niaid.nih.gov/news-events/bu…
2/A poor effort at patient outreach may have contributed to this outcome, as well as US incompetence with respect to rapid testing of symptomatic subjects. But the likely main factor: Our media and "medical experts" have convinced most Americans that HCQ is toxic and useless.
3/Case series in Marseilles, New York, and Sao Paolo reported only 29 deaths in 3,871 patients given this regimen - a case-fatality rate of only 0.7%. (Zelenko in NY, who added zinc, had a CFR under 0.2%.) By comparison, CFR is 4% in Germany, which tests extensively.
Read 8 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us on Twitter!

:(