6 ms·

There's a nice diagram from Science that shows how Remdesivir and other potential anti-coronavirus drugs work: https://science.sciencemag.org/content/sci/368/64

by kens 6y ago

There's a nice diagram from Science that shows how Remdesivir and other potential anti-coronavirus drugs work: https://science.sciencemag.org/content/sci/368/6493/829/F1.large.jpg https://science.sciencemag.org/content/sci/368/6493/829/F1.l...

acqq 6y ago
The picture is from https://science.sciencemag.org/content/368/6493/829 https://science.sciencemag.org/content/368/6493/829 published "22 May 2020" at the time when less was known about Chloroquine and hydroxychloroquine than today about treating Covid-19 (1). That's the needed perspective when watching the picture, where the rest is still relevant. ----- 1) E.g. June 23, 2020 "NIH: Trial Investigating Hydroxychloroquine for COVID-19 Stopped" https://www.empr.com/home/news/hydroxychloroquine-trial-halted-unlikely-to-benefit-covid19-patients/ https://www.empr.com/home/news/hydroxychloroquine-trial-halt... 17 June 2020 "“Solidarity” clinical trial" https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments https://www.who.int/emergencies/diseases/novel-coronavirus-2... "hydroxychloroquine does not result in the reduction of mortality of hospitalised COVID-19 patients, when compared with standard of care." And before, Jun. 9, 2020: "Three big studies dim hopes that hydroxychloroquine can treat or prevent COVID-19": https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-hydroxychloroquine-can-treat-or-prevent-covid-19 https://www.sciencemag.org/news/2020/06/three-big-studies-di...
- jakeogh 6y ago
  https://aapsonline.org/preliminary-injunction-sought-to-release-hydroxychloroquine-to-the-public/ https://aapsonline.org/preliminary-injunction-sought-to-rele... more: https://news.ycombinator.com/item?id=23405435 https://news.ycombinator.com/item?id=23405435 and: https://defyccc.com/another-junk-anti-hydroxychloroquine-study-2/ https://defyccc.com/another-junk-anti-hydroxychloroquine-stu...
  - acqq 6y ago
    From that link: "AAPS files with the court a chart showing how countries that encourage HCQ use, such as South Korea, India, Turkey, Russia, and Israel, have been far more successful in combatting COVID-19 than countries that have banned or discouraged early HCQ use, as the FDA has." However: that chart is totally misleading, it's a typical "non sequitur". "Case fatality rate" is just a ratio "death" through "cases". Where those with weaker symptoms are recognized as "cases" the rate is lower. How they are recognized is not the same across different countries.
    - jakeogh 6y ago
      Agreed. Excess mortality is the real measure. Note, you seem to be posting studies that did not pair HCQ with zinc, _and_ are not using it prophylactically. Is my understanding correct? For example: https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-hydroxychloroquine-can-treat-or-prevent-covid-19 https://www.sciencemag.org/news/2020/06/three-big-studies-di... links to https://www.recoverytrial.net/files/hcq-recovery-statement-050620-final-002.pdf https://www.recoverytrial.net/files/hcq-recovery-statement-0... which does not mention zinc, and it's patients admitted to the hospital (not prophylactic). Digging further, to the source given in that pdf, not a mention of zinc: https://www.recoverytrial.net/@@search?SearchableText=zinc https://www.recoverytrial.net/@@search?SearchableText=zinc which is the whole point of using HCQ in the first place.
      - acqq 6y ago
        > you seem to be posting studies that did not pair HCQ with zinc I'm just posting studies that were the basis for what FDA decided June 15, 2020 (1): "FDA has revoked the emergency use authorization (EUA) to use hydroxychloroquine and chloroquine to treat COVID-19 in certain hospitalized patients when a clinical trial is unavailable or participation is not feasible. We made this determination based on recent results from a large, randomized clinical trial in hospitalized patients that found these medicines showed no benefit for decreasing the likelihood of death or speeding recovery." And I don't have more information than that. 1) https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or https://www.fda.gov/drugs/drug-safety-and-availability/fda-c...
- highmastdon 6y ago
  Is any of these studies using Zinc? We know that a lot of people have both Vitamin D and Zinc deficiency. How HCQ works is to transport the Zinc into the cell so that Zinc can stop the RNA replication. (I’m a layman here, but it’s what I’ve managed to understand after deliberate research) Thus, HCQ without Zinc is like using a bucket but forgetting the water to stop the fire. Just throwing buckets at the fire isn’t gonna work much when there’s no water in the bucket. Have a look at this [1] studies that shows around a 9% less mortality when treated with Zinc and a even more when treated EARLY with HCQ PLUS Zinc. (Please take a look at the numbers in the last table, it’s very clear that HCQ + Zinc reduces mortality) [1]: https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1.full.pdf https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
  - jbritton 6y ago
    I think there are 2 hypothesis for HCQ. One is that it blocks autophagosome-lysosome fusion. The second is that it is a Zinc ionophore, which enables Zinc to enter cells to stop viral replication. It seems that almost all the studies are not using Zinc. Here is a retrospective observational study showing effectiveness of HCQ+Zinc. It is a mystery to me why this second path doesn’t get more attention. Quercetin is also a Zinc ionophore. So Quercetin+Zinc should also be studied. https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1 https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
    - waveforms 6y ago
      This recent research from China suggest another possibility..that it acts as an ACE2 blocker. https://www.biorxiv.org/content/10.1101/2020.06.22.164665v1.full https://www.biorxiv.org/content/10.1101/2020.06.22.164665v1....
    - gridlockd 6y ago
      The problem is that this crank doctor from France used exactly this treatment (Zinc+HCQ) in a crappy study and proclaimed it as hugely successful. This was then picked up by a crowd of "right wing deplorables" up to and including the orange man in the white house. The scientific establishment can not allow this bunch of clowns to turn out right, thus further inquiry is being suppressed. Call it a conspiracy theory, but that's exactly how human egos have played a role in the history of science.
divbzero 6y ago
Where does dexamethasone fit in? Does it target part of the viral lifecycle or simply treat the effects?
- acqq 6y ago
  https://www.nature.com/articles/d41586-020-01824-5 https://www.nature.com/articles/d41586-020-01824-5 "The [steroid] drugs suppress the immune system, which could provide some relief for patients whose lungs are ravaged by an overactive immune response that sometimes manifests in severe cases of COVID-19. But such patients may still need a fully functioning immune system to fend off the virus itself." "no effect on mild infections" Basically if taken too early it does the wrong action, but it helps some of those already on oxygen. And it's cheap.
  - Gibbon1 6y ago
    It's like what a friends brother (cardiac surgeon) said about clot busting drugs. That knife is sharp on both sides.
- CyanLite2 6y ago
  The first week or two, your immune system ramps up to fight the infection. During this battle, the collateral damage is what gives you symptoms like joint pain, runny nose, sore throat, etc. Near the 3rd week of infection, 85% of patients are recovering and feeling better because their immune response has naturally turned itself off. For some reason, this doesn't happen in about 15% of patients. We call this a 'cytokine storm'. This is where your immune system has gone nuclear and is still destroying anything and everything it sees, including normal healthy tissue. This can ultimately lead to multi-organ failure and death if it can't be stopped. Dexamethasone tamps down that immune response, allowing your body to heal. Obviously it has to be timed right. It doesn't do anything to the virus, only your immune response.
  - __blockcipher__ 6y ago
    To connects the dots, pathological cytokine release syndrome is highly likely to be causing the (extremely rare) instances of stroke in non-elderly COVID-19 patients, organ damage, etc. I get incredibly annoyed when people act like (a) these strokes / organ damage are happening in significant quantities and (b) that it’s unique to SARS-2

by kens 6y ago

acqq 6y ago

The picture is from https://science.sciencemag.org/content/368/6493/829 https://science.sciencemag.org/content/368/6493/829 published "22 May 2020" at the time when less was known about Chloroquine and hydroxychloroquine than today about treating Covid-19 (1). That's the needed perspective when watching the picture, where the rest is still relevant. ----- 1) E.g. June 23, 2020 "NIH: Trial Investigating Hydroxychloroquine for COVID-19 Stopped" https://www.empr.com/home/news/hydroxychloroquine-trial-halted-unlikely-to-benefit-covid19-patients/ https://www.empr.com/home/news/hydroxychloroquine-trial-halt... 17 June 2020 "“Solidarity” clinical trial" https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments https://www.who.int/emergencies/diseases/novel-coronavirus-2... "hydroxychloroquine does not result in the reduction of mortality of hospitalised COVID-19 patients, when compared with standard of care." And before, Jun. 9, 2020: "Three big studies dim hopes that hydroxychloroquine can treat or prevent COVID-19": https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-hydroxychloroquine-can-treat-or-prevent-covid-19 https://www.sciencemag.org/news/2020/06/three-big-studies-di...

jakeogh 6y ago
https://aapsonline.org/preliminary-injunction-sought-to-release-hydroxychloroquine-to-the-public/ https://aapsonline.org/preliminary-injunction-sought-to-rele... more: https://news.ycombinator.com/item?id=23405435 https://news.ycombinator.com/item?id=23405435 and: https://defyccc.com/another-junk-anti-hydroxychloroquine-study-2/ https://defyccc.com/another-junk-anti-hydroxychloroquine-stu...
- acqq 6y ago
  From that link: "AAPS files with the court a chart showing how countries that encourage HCQ use, such as South Korea, India, Turkey, Russia, and Israel, have been far more successful in combatting COVID-19 than countries that have banned or discouraged early HCQ use, as the FDA has." However: that chart is totally misleading, it's a typical "non sequitur". "Case fatality rate" is just a ratio "death" through "cases". Where those with weaker symptoms are recognized as "cases" the rate is lower. How they are recognized is not the same across different countries.
  - jakeogh 6y ago
    Agreed. Excess mortality is the real measure. Note, you seem to be posting studies that did not pair HCQ with zinc, _and_ are not using it prophylactically. Is my understanding correct? For example: https://www.sciencemag.org/news/2020/06/three-big-studies-dim-hopes-hydroxychloroquine-can-treat-or-prevent-covid-19 https://www.sciencemag.org/news/2020/06/three-big-studies-di... links to https://www.recoverytrial.net/files/hcq-recovery-statement-050620-final-002.pdf https://www.recoverytrial.net/files/hcq-recovery-statement-0... which does not mention zinc, and it's patients admitted to the hospital (not prophylactic). Digging further, to the source given in that pdf, not a mention of zinc: https://www.recoverytrial.net/@@search?SearchableText=zinc https://www.recoverytrial.net/@@search?SearchableText=zinc which is the whole point of using HCQ in the first place.
    - acqq 6y ago
      > you seem to be posting studies that did not pair HCQ with zinc I'm just posting studies that were the basis for what FDA decided June 15, 2020 (1): "FDA has revoked the emergency use authorization (EUA) to use hydroxychloroquine and chloroquine to treat COVID-19 in certain hospitalized patients when a clinical trial is unavailable or participation is not feasible. We made this determination based on recent results from a large, randomized clinical trial in hospitalized patients that found these medicines showed no benefit for decreasing the likelihood of death or speeding recovery." And I don't have more information than that. 1) https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or https://www.fda.gov/drugs/drug-safety-and-availability/fda-c...
highmastdon 6y ago
Is any of these studies using Zinc? We know that a lot of people have both Vitamin D and Zinc deficiency. How HCQ works is to transport the Zinc into the cell so that Zinc can stop the RNA replication. (I’m a layman here, but it’s what I’ve managed to understand after deliberate research) Thus, HCQ without Zinc is like using a bucket but forgetting the water to stop the fire. Just throwing buckets at the fire isn’t gonna work much when there’s no water in the bucket. Have a look at this [1] studies that shows around a 9% less mortality when treated with Zinc and a even more when treated EARLY with HCQ PLUS Zinc. (Please take a look at the numbers in the last table, it’s very clear that HCQ + Zinc reduces mortality) [1]: https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1.full.pdf https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
- jbritton 6y ago
  I think there are 2 hypothesis for HCQ. One is that it blocks autophagosome-lysosome fusion. The second is that it is a Zinc ionophore, which enables Zinc to enter cells to stop viral replication. It seems that almost all the studies are not using Zinc. Here is a retrospective observational study showing effectiveness of HCQ+Zinc. It is a mystery to me why this second path doesn’t get more attention. Quercetin is also a Zinc ionophore. So Quercetin+Zinc should also be studied. https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1 https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v...
  - waveforms 6y ago
    This recent research from China suggest another possibility..that it acts as an ACE2 blocker. https://www.biorxiv.org/content/10.1101/2020.06.22.164665v1.full https://www.biorxiv.org/content/10.1101/2020.06.22.164665v1....
  - gridlockd 6y ago
    The problem is that this crank doctor from France used exactly this treatment (Zinc+HCQ) in a crappy study and proclaimed it as hugely successful. This was then picked up by a crowd of "right wing deplorables" up to and including the orange man in the white house. The scientific establishment can not allow this bunch of clowns to turn out right, thus further inquiry is being suppressed. Call it a conspiracy theory, but that's exactly how human egos have played a role in the history of science.

divbzero 6y ago

Where does dexamethasone fit in? Does it target part of the viral lifecycle or simply treat the effects?

acqq 6y ago
https://www.nature.com/articles/d41586-020-01824-5 https://www.nature.com/articles/d41586-020-01824-5 "The [steroid] drugs suppress the immune system, which could provide some relief for patients whose lungs are ravaged by an overactive immune response that sometimes manifests in severe cases of COVID-19. But such patients may still need a fully functioning immune system to fend off the virus itself." "no effect on mild infections" Basically if taken too early it does the wrong action, but it helps some of those already on oxygen. And it's cheap.
- Gibbon1 6y ago
  It's like what a friends brother (cardiac surgeon) said about clot busting drugs. That knife is sharp on both sides.
CyanLite2 6y ago
The first week or two, your immune system ramps up to fight the infection. During this battle, the collateral damage is what gives you symptoms like joint pain, runny nose, sore throat, etc. Near the 3rd week of infection, 85% of patients are recovering and feeling better because their immune response has naturally turned itself off. For some reason, this doesn't happen in about 15% of patients. We call this a 'cytokine storm'. This is where your immune system has gone nuclear and is still destroying anything and everything it sees, including normal healthy tissue. This can ultimately lead to multi-organ failure and death if it can't be stopped. Dexamethasone tamps down that immune response, allowing your body to heal. Obviously it has to be timed right. It doesn't do anything to the virus, only your immune response.
- __blockcipher__ 6y ago
  To connects the dots, pathological cytokine release syndrome is highly likely to be causing the (extremely rare) instances of stroke in non-elderly COVID-19 patients, organ damage, etc. I get incredibly annoyed when people act like (a) these strokes / organ damage are happening in significant quantities and (b) that it’s unique to SARS-2