Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

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  • Wed, Aug 05, 2020 - 09:42pm

    #1
    iLoveFacts

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    Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

I have been sharing HCQ info with some friends to bring their awareness to it. We are having an open discussion on the topic, and one brought this article to my attention. I could not find mention of it here.

I haven’t had a chance to fully review and digest, but I have a few questions:
– If HCQ doesn’t prevent infection in lung cells, what other mechanisms could explain it’s good results in so many places?
– I don’t know anything about the cell lines, but I’m wondering how relevant they are

https://www.nature.com/articles/s41586-020-2575-3

https://www.nature.com/articles/s41586-020-2575-3_reference.pdf

7/22/20 Preprint article

Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2

Abstract
The COVID-19 pandemic, which is caused by the novel coronavirus SARS-CoV-2, has been associated with more than 470,000 fatal cases worldwide. In order to develop antiviral interventions quickly, drugs used for treatment of unrelated diseases are currently being repurposed to combat COVID-19. Chloroquine is a anti-malaria drug that is frequently employed for COVID-19 treatment since it inhibits SARS-CoV-2 spread in the kidney-derived cell line Vero1–3. Here, we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. Moreover, we report that chloroquine does not block SARS-CoV-2 infection of the TMPRSS2-positive lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not operative in lung cells and is unlikely to protect against SARS-CoV-2 spread in and between patients.

  • Thu, Aug 06, 2020 - 03:46am

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    davefairtex

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    HCQ doesn’t block infection of a lung-cancer-cell line

Ok, let’s read it carefully.  Article says:

Moreover, we report that chloroquine does not block SARS-CoV-2 infection of the TMPRSS2-positive lung cell line Calu-3. These results indicate that chloroquine targets a pathway for viral activation that is not operative in lung cells and is unlikely to protect against SARS-CoV-2 spread in and between patients.

So what is cell line Calu-3?

https://en.wikipedia.org/wiki/Calu-3

Calu-3 is a human lung cancer cell line commonly used in cancer research and drug development. Calu-3 cells are epithelial and can act as respiratory models in preclinical applications.[1]

So, HCQ apparently allows SC2 to infect cancerous lung cells.

Does HCQ protect normal lung cells?  That seems like a more important question.

I have read that cancer cells operate under different rules – they make sure to transport zinc out of the cancer cell, among other odd things.  So perhaps HCQ acts differently with them than with normal cells.

Why did they select this particular cell line?  It would seem to be an odd choice.  It reminds me of when they gave toxic doses of HCQ to half-dead patients in the Oxford RECOVERY trial and then proclaimed higher mortality.

File this one under “nice try, Pharma.”

  • Thu, Aug 06, 2020 - 06:06am

    #3
    Kathy

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    Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

As I understand it, it is the zinc that blocks the viral replication.  The only thing the HCQ does is get the zinc into the cells.

 

I don’t think this study shows us anything we care about.

  • Thu, Aug 06, 2020 - 09:16am

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    davefairtex

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    a bunch of things

According to a lecture by one of those “front line doctors”, there were about 5 different things that HCQ did that helped stop the virus.  It wasn’t just zinc.  I didn’t know this prior to this lecture.

 

 

  • Thu, Aug 06, 2020 - 09:31am

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    Jim H

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    Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

  • Fri, Aug 07, 2020 - 09:03am

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    tbp

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    Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

^ Interesting table from Dr. Shiva, what video is that from?

  • Sun, Aug 09, 2020 - 02:16am

    #7
    peakabu

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    Other HCQ’s Effects

@Kathy @davefairtex

According to this study, HCQ apparently have the following additional effects other than acting as a zinc ionophore:

  1. It can change the pH at the surface of the cell membrane and, thus, inhibit the fusion of the virus to the cell membrane
  2. It can also inhibit nucleic acid replication, glycosylation of viral proteins, virus assembly, new virus particle transport, virus release, and other processes to achieve its antiviral effects
  3. It may have an “immunomodulatory effect… [that] may be useful in controlling the cytokine storm”

However, the 3rd effect may not be true as HCQ doesn’t appear to be effective when administered late, and people don’t usually experience cytokine storm until the disease becomes too serious. Please correct me if I’m wrong. Or does it only help prevent a cytokine storm?

 

  • Sun, Aug 09, 2020 - 07:58am

    #8
    tbp

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    Pre-print Nature article says HCQ doesn’t inhibit infection in lung cells

I almost stopped reading when I saw “Currently, there is no evidence to support the use of hydroxychloroquine in SARS-CoV-2 infection.” LOL.

How can it “inhibit nucleic acid replication, glycosylation of viral proteins, virus assembly, new virus particle transport, virus release, and other processes to achieve its antiviral effects” — all of that, how?

  • Sun, Aug 09, 2020 - 09:31am

    #9

    Jim H

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    Dr. Shiva A. video link for tdp

I found the original video that I grabbed the HCQ frame from and my link should start the video at the appropriate timestamp;

Shiva is an MIT PhD who developed a modelling tool called Cytosolve that looks at the systemic effects of various compounds (drugs, supplements, etc).

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