Article

2022-09-18 Science & Technology

Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture

[Why HCQ and Ivermectin were/still are demonized: If there is an alternative therapy, Big Pharma may not get Emergency Use Authorizations (EUAs).]
[Nature dot com] Abstract:

Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ’s mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters—erythromycin has a similar effect. We conclude HCQ inhibits viral entry through two distinct mechanisms in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy.

Posted by DooDahMan 2022-09-18 08:35|| || Front Page|| [21 views ] Top

#1 This my vriends, is a non-trivial discovery.

Posted by Besoeker 2022-09-18 09:08|| 2022-09-18 09:08|| Front Page Top

#2 I'm still wondering what might have happened if Trump never mentioned HCQ or ivermectin.

Posted by M. Murcek 2022-09-18 09:15|| 2022-09-18 09:15|| Front Page Top

#3 And talk about "safe and effective", HCQ and Ivermectin are about as good as it gets.

Posted by DooDahMan 2022-09-18 09:43|| 2022-09-18 09:43|| Front Page Top

#4 The combination of Big Pharma with gummint mandates is classic fascism. Just done informally because emergency of hysteria.

Posted by M. Murcek 2022-09-18 10:00|| 2022-09-18 10:00|| Front Page Top

#5 Neil Cavuto: "HCQ will KILL YOU! Reeee!"

Posted by Frank G 2022-09-18 10:56|| 2022-09-18 10:56|| Front Page Top

#6 There are possibly as many reasons NOT to watch Fox as there are to watch Fox. Maybe.

Posted by DooDahMan 2022-09-18 10:59|| 2022-09-18 10:59|| Front Page Top

#7 I gave up on FauxNews years ago.

Posted by M. Murcek 2022-09-18 11:09|| 2022-09-18 11:09|| Front Page Top

#8
SO....
HCQ which was already " generic for Plaquenil " / Cheap and in plentiful global supply and did a better job.

But using it would have precluded using a surprisingly quickly developed, almost as if PLANNED FOR, experimental vaxccident with secretly known adverse side effects.

Thus allowing Governments to spend $100's of Billions of dollars on a poorly working VAX that made certain insider people Uber rich. Plus, by current USC laws, are not required to state or acknowledge background cash awards collected from companies for their insider Taxpayer funded R&D gain of function projects.

Sounds like charges of Mass Murder for the deaths of 6,530,581+ in a International Criminal Court should be happening.

But who controls the International Criminal Court (ICC).
A court of last resort for the prosecution of serious international crimes, including genocide, war crimes, and crimes against humanity.

USA – Not a party
Russia – Not a party
China – Not a Party
UK – a member BUT ensured, in domestic legislation incorporating the ICC Statute, that no criminal proceedings may be initiated without the consent of the UK Government which consent had never been granted, to any private prosecutor, whether under the ICC or under any other legislation on International crime.

Posted by NN2N1 2022-09-18 11:11|| 2022-09-18 11:11|| Front Page Top

#9 Ivermectin does the same thing.

Posted by Deacon Blues 2022-09-18 11:44|| 2022-09-18 11:44|| Front Page Top

#10 There are people who need to be brought to account and punished.

The ICC? No thanks...

Posted by M. Murcek 2022-09-18 11:46|| 2022-09-18 11:46|| Front Page Top

#11 People wondered through out the pandemic why the population wasn’t dropping dead in the streets

Common sense says that invermectin is an anti parasitic guy and HCQ is a preventative treatment for malaria

So the short answer is that most people in Equitorial Africa have maintenance doses of one or both drugs in their system

Posted by Sock Puppet of Doom 2022-09-18 12:35|| 2022-09-18 12:35|| Front Page Top

#12 I'm still wondering what might have happened if Trump never mentioned HCQ or ivermectin.

There's lots of other helpful drugs Trump didn't mention that wound up being withheld from Covid patients anyway.

Off the top of my head: ACE inhibitors, Azithromycin, Antihistamines, and Aspirin.

It's kind of awe-inspiring in its chickenshitness, The guy who said that most people who died from the Spanish flu died from secondary infections was also the one who made damn sure no antibiotic was part of the treatment protocol for Covid.

Posted by Fester Platypus3060 2022-09-18 13:03|| 2022-09-18 13:03|| Front Page Top

#13 Oh, BTW, that last comment was from me. I'll worry about my real nick later, I'm on lunch break.

(Who knew the apocalypse was going to have a lunch break?)

Posted by Your Friendly Neighborhood Snowy Thing 2022-09-18 13:05|| 2022-09-18 13:05|| Front Page Top

#14 A court of last resort for the prosecution of serious international crimes, including genocide, war crimes, and crimes against humanity.

USA – Not a party
Russia – Not a party
China – Not a Party

The ICC is under the control of the Security Council (SC)
That means they can control the Court but are themselves unanswerable to it!
This is why the ICC has been mainly indicting Africans.

Posted by ACA JOE 2022-09-18 18:44|| 2022-09-18 18:44|| Front Page Top

#15 SPOD: some equatorial Africans will have maintenance doses of malaria suppressants, but most won't. There can be side effects, and money is tight.
And while anti-helmintics are often given to patients automatically, their effect seems to wear off after a relatively short time, so they must not stay in the blood more than a few weeks (see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341313/ , assuming that mules metabolize the stuff similarly to humans).
Bottom line--I don't expect much of either of these in their blood.

Posted by James 2022-09-18 23:07|| https://idontknowbut.blogspot.com 2022-09-18 23:07|| Front Page Top

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