Scientific basis of the use of Ivermectin and many other zinc ionophores (plus other useful chemical species) in COVID-19

[-] Murky-Lengthiness | 4 points | Jul 13 2020 03:28:42

Soporte científico del protocolo de tratamiento del Dr. Covid Ver2 7/12/2020 El equipo de investigación al que pertenece el Dr. Covid postulo desde hace muchos meses que los ionoforos del zinc son antivirales de amplio espectro. Un ionoforo de zinc es una sustancia que ayuda a transportar el zinc a través de la membrana citoplásmica y aumenta el nivel de zinc dentro de las células. Este es otro mecanismo a través del cual se puede ayudar a reducir la carga viral y la gravedad de las infecciones virales. Un estudio realizado por el Instituto Nacional de Salud (NIH) también mostró que la suplementación con zinc disminuye la morbilidad de la infección del tracto respiratorio inferior en pacientes pediátricos en el mundo en desarrollo. Un mayor nivel de zinc intracelular a su vez inhibe el ARN polimerasas dependientes de ARN (RdRp) responsables de la replicación viral. Las polimerasas son enzimas capaces de transcribir o replicar ácidos nucleicos, por lo que resultan cruciales en la división celular y en la transcripción del ADN. Dicho de otra forma, sin esta fotocopiadora, la fábrica de replicación del virus dentro de una célula no funciona. Dada su decisiva función en el ciclo replicativo vírico, las polimerasas son objetivos clave para la investigación antiviral. La polimerasa está embebida en un complejo asociado a la membrana de la célula hospedante formado a partir del ARN vírico y de proteínas procedentes del propio virus y de la célula hospedante. Desde hace diez años se sabía que el incremento de las concentraciones intracelulares del ion zinc, al interferir con la correcta formación de las proteínas virales (incluidas las polimerasas), dificultan eficazmente la replicación de varios virus ARN, entre otros los coronavirus

Además de los ya mencionados, indicamos diversos estadios de replicación viral que son inhibidos por el zinc. Las investigaciones in vitro han demostrado varios mecanismos a través de los cuales el zinc interfiere con el ciclo de la replicación viral. Estos incluyen: 1 la inactivación de los virus libres. 2 la inhibición de la eliminación del recubrimiento viral. 3 la transcripción del genoma viral. 4 la inhibición de la traducción de la proteína viral y el procesamiento de la poliproteina. 5 inhibición de la liberación del virus en su camino al lisosoma y en el lisosoma mismo a través del aumento del ph del medio. CV, coronavirus; DdDp, DNA-dependent DNA polymerase; EMCV, encephalomyocarditis virus; FMDV, foot and mouth disease virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HPV, human papilloma virus; HRV, human rhinovirus; HSV, herpes simplex virus; PV, polio virus; RdRp, RNA-dependent RNA polymerase; RT, reverse transcriptase; SARS, severe acute respiratory syndrome coronavirus; SFV, Semliki Forest virus; SV, sindbis virus; VZV, varicella-zoster virus; Zn, zinc. El zinc tiene propiedades antivirales comprobadas y puede reducir la duración del resfriado en un 33 %. Los científicos señalan que existen indicios de que mantener niveles óptimos de zinc puede reducir la gravedad del COVID-19. Se ha observado que el zinc tiene un efecto antiviral frente al coronavirus, modificando el pH de unos orgánulos de la célula, los lisosomas, donde se multiplica el virus. El zinc ha demostrado tener la capacidad de inhibir la reproducción del virus SARS-CoV-2 en el laboratorio, lo que los nosotros creemos que es un efecto terapéutico subyacente del uso de los ionoforos (y en muchos otros virus como el dengue, Zika, HIV, etc). El zinc también puede regular ascendentemente la producción de interferón y la actividad antiviral de la proteína. Sugieren que también puede reducir el riesgo de una infección bacteriana secundaria, en especial el Streptococcus pneumoniae. El zinc es una deficiencia común en adultos mayores, y en personas que tienen obesidad, diabetes o aterosclerosis. Y no es casualidad que este es el mismo grupo de personas que tienen un mayor riesgo de complicaciones por SARS-CoV-2. El equipo de investigación que analizó estudios anteriores sobre el zinc sugiere que tiene un efecto protector contra el COVID-19 al reducir la inflamación, eliminar la mucosidad, prevenir el daño provocado por el ventilador y respaldar el sistema inmunológico. Entre los ionoforos de zinc se encuentran antiparasitarios, antifungales, antiamibianos, antioxidantes fenolicos, etc. Por lo que sabemos que además de la ivermectina también funcionan (junto con el zinc) la nitazoxanida, el metronidazol, la quinfamida y el mebendazol (vermox plus), el tinidazol, la Oleuropeina, el Pterostilbeno, etc. Los artesunatos (artemisinina por ejemplo) también funcionan al igual que los amantadatos (amantadina por ejemplo pero a dosis correctas), etc.

Figura - Los mecanismos de protección propuestos del zinc en COVID-19. 1. El zinc mejora significativamente la morfología de los cilios (54) y aumenta la frecuencia del latido ciliar (55), mejorando así el aclaramiento mucociliar y la eliminación de bacterias y partículas que contienen virus. Al regular las proteínas de unión estrecha ZO-1 y claudina-1 (57) y aumentar la actividad antioxidante del epitelio respiratorio (56), el zinc también aumenta la función de barrera de este último. A su vez, se demostró que la infección por coronavirus afecta el aclaramiento mucociliar (50) y predispone al pulmón para una mayor agresión viral y bacteriana. 2. El zinc también puede poseer actividad antiviral a través de la inhibición de RdRp y el bloqueo de la replicación adicional de ARN viral como se demostró para el SARS-CoV (38). La evidencia indirecta también indica que Zn2 + puede disminuir la actividad de ACE2 (49), que se sabe que es el receptor del SARS-CoV-2 (47). 3. La modulación de la inmunidad antiviral por zinc también puede limitar la infección por SARS-CoV-2 al menos a través de la regulación positiva de la producción de IFNα (63) y el aumento de su actividad antiviral (64). Este último puede estar mediado por la señalización JAK1 / STAT1 inducida por IFNα y la regulación positiva de proteínas antivirales (RNaseL y PKR) que se sabe que degradan el ARN viral e inhiben su traducción (65).

Se sabe que la respuesta inflamatoria excesiva que resulta en la sobreproducción de citocinas proiflamatorias y tormentas de citocinas desempeña un papel importante en la patogénesis de COVID-19 (103). A su vez, el zinc posee actividad antiinflamatoria a través de la inhibición de la actividad de IKK y la posterior señalización de NF-κB que resulta en una baja regulación de la producción de citocinas proinflamatorias (122,124). La modulación de las funciones reguladoras de las células T por zinc también puede limitar la respuesta inflamatoria excesiva (125,126), así como la regulación a la baja de la producción de citocinas proinflamatorias (127,123).
Dado el alto riesgo de coinfección bacteriana en la neumonía viral (128), la inhibición inducida por Zn del crecimiento de S. pneumoniae a través de la modulación de la homeostasis bacteriana del Mn (II) (137) también puede ser beneficiosa.
El estado del zinc también se asocia con factores de riesgo de mortalidad alta por COVID-19. Específicamente, se sabe que el envejecimiento, la inmunodeficiencia, así como las enfermedades metabólicas como la obesidad, la diabetes y la aterosclerosis, son factores de riesgo de mortalidad por enfermedad alta (31,32) y deficiencia de zinc (149). A su vez, la suplementación con Zn puede tener un efecto beneficioso en la modulación de al menos algunos de estos factores de riesgo. ACE2, enzima convertidora de angiotensina 2; IFN, interferón; IKK, IκB quinasa; NF-κB, factor nuclear-κB; SDRA, síndrome de dificultad respiratoria aguda.

[-] thaw4188 | 2 points | Jul 14 2020 00:32:34

auto-translation to english

https://translate.google.com/translate?sl=es&tl=en&u=https://www.redditmedia.com/r/ivermectin/comments/hq7x93/scientific_basis_of_the_use_of_ivermectin_and/fxw8ko8/?embed=true

[-] Murky-Lengthiness | 1 points | Jul 16 2020 09:26:07

Thank you for the translation! Could you please post this in the main Reddit Covid? I can only post links. R/coronavirus

[-] Murky-Lengthiness | 2 points | Jul 13 2020 03:28:05

How do I post PDF’s?

[-] BuscadorDaVerdade | 2 points | Jul 13 2020 09:52:20

You can post a link to a PDF. If you have the file but no link, maybe upload it to a file sharing site.

[-] TrumpLyftAlles | 1 points | Aug 18 2020 22:49:28

Presumably you found the PDF on a web site someplace. If there's an abstract and the PDF is available by clicking a [Download] button, then try right-clicking on the button and selecting "Copy Link Address" (in Chrome, IDK other browsers). Plug the thus-copied link into the browser and see if it gets you the PDF. Then post that link to the sub.

I personally dislike links that start downloading PDFs, but sometimes they're unavoidable.

If you have a page with an abstract or other significant textual description of the PDF and that page has a link to the PDF, just post that page as the link for the post, include the abstract in your write up, and mention in your write-up that there's a link to the PDF on the posted page.

If the PDF is on your PC and you don't remember where you found it, try searching for the title. That will probably bring you to a place where you can find a download link.

If it's on your PC and you can't find a link on the web, then you can try posting it to a site that hosts papers. Google docs works for everyone, I think. I tried SCRIBD with mixed results: once, no problems, but another time it seemed like only I could see the document.

Let me know if none of this works.

[-] thaw4188 | 2 points | Jul 14 2020 00:24:21

but is ivermectin really a zinc ionosphore?

I've not seen the chemical map that proves that.

I only have read quercetin and EGCG are weak ionophores, note both substances have some risk at significant quantity, but I think mostly their action is from blocking iron absorption which competes with zinc absorption so zinc is processed better

someone has also claimed monolaurin is a weak ionosphere, I have no proof

I've tried all of those in desperation btw among the past seven weeks, only ivermectin actually did anything

I don't think it's the zinc, yes you need zinc in your system for immune to work properly but megadose is useless once sick

[-] Murky-Lengthiness | 1 points | Jul 14 2020 05:17:27

It is, when two molecules of it form a complex in vivo

[-] TrumpLyftAlles | 1 points | Aug 18 2020 22:57:08

Murky, can you come up with a link? I mean, you're a wonderful person and all, but your saying so doesn't make it so. (<-- this is supposed to be a light, friendly remark.)

[-] Murky-Lengthiness | 1 points | Jul 14 2020 05:19:58

Quercetin and EGCG are useless precisely because they are weak ionophores, Hydrochloroquine only worked with zinc. It IS the zinc

[-] thaw4188 | 1 points | Jul 14 2020 11:10:07

I wish I could see a table of strengths and why on a molecular level

I've never seen a ranking and I did always suspect the one single saving grace of HCQ was it's zinc ionophore ability, it has too many other downsides

this computer modeling kinda gives it away

https://i.imgur.com/jY1mhvy.png

look how strong ivermectin vs HCQ/CQ hydroxychloroquine/chloroquine

[-] stiveooo | 1 points | Jul 17 2020 23:07:39

Where did you got the image?

[-] thaw4188 | 1 points | Jul 18 2020 00:50:19

sorry I've lost the original link but it's from one of the great studies TLA has linked in the sub, it was buried in the paper and I knew it was a great one to save

there are other computer modeling studies that look quite similar but that chart is very complete except for some really new stuff

[-] thaw4188 | 1 points | Jul 14 2020 14:55:23

another followup on this crossed my mind before I forget

zinc is apparently not zinc zinc zinc, ie. not all formulas/sources are the same

now I really want to see a molecular map but there are some claims this kind of zinc absorbs far more readily than others

https://www.amazon.com/gp/product/B015NZBF96/

(I've not tried it, not an endorsement, just interesting)

https://www.healthline.com/nutrition/zinc-supplements#types
Zinc gluconate: As one of the most common over-the-counter forms of zinc, zinc gluconate is often used in cold remedies, such as lozenges and nasal sprays (2).
Zinc acetate: Like zinc gluconate, zinc acetate is often added to cold lozenges to reduce symptoms and speed up the rate of recovery (3).
Zinc sulfate: In addition to helping prevent zinc deficiency, zinc sulfate has been shown to reduce the severity of acne (4).
Zinc picolinate: Some research suggests that your body may absorb this form better than other types of zinc, including zinc gluconate and zinc citrate (5).
Zinc orotate: This form is bound to orotic acid and one of the most common types of zinc supplements on the market (6).
Zinc citrate: One study showed that this type of zinc supplement is as well-absorbed as zinc gluconate but has a less bitter, more appealing taste (7).

[-] Murky-Lengthiness | 1 points | Jul 15 2020 02:11:57

Thank you for all the very useful information and hypothesis.

[-] TrumpLyftAlles | 1 points | Aug 18 2020 22:53:26

Zinc gluconate lozenges

I suck on a few of these every day.

is as well-absorbed as zinc gluconate but has a less bitter, more appealing taste (7).

The gluconate lozenges I bought are actually too tasty, I'm tempted to consume too many because they're tasty.

[-] thaw4188 | 2 points | Aug 18 2020 22:55:28

I am not sure constant presence of zinc is healthy, in fact it may be the opposite

you cannot absorb iron when zinc is present, they compete

you really need an iron/ferritin test to make sure you don't become anemic

zinc should probably be taken all at once, once a day, 12 hours apart from iron

[-] TrumpLyftAlles | 1 points | Aug 18 2020 23:04:17

ferritin

Thanks for the heads up. I have long believed that too much iron increases risk of heart attack. (Have we discussed this before?) So I'm good with low iron. I have an doctor's appointment to get blood work, so I'll find out then whether it's a problem.

I thought less iron meant fewer covid-19 complications too, but this contradicts that:

The primary outcome, all-cause mortality, was observed in 265 (28.1%) patients. Patients who died had a significantly higher median admission and maximum ferritin levels than those who did not. However, death was poorly predicted by admission and maximum ferritin levels on receiver operator curve (ROC) analysis, with AUCs of 0.677 and 0.638, respectively.

I still don't get AUCs. :(

[-] thaw4188 | 1 points | Aug 18 2020 23:05:25

yeah everyone likes to quote that study

except if iron caused heart problems, endurance athletes would be constantly dropping dead, instead they have far better health and longer lives than the average population

you cannot have healthy red blood cells without proper iron and iron levels take forever to correct

[-] TrumpLyftAlles | 1 points | Aug 18 2020 23:11:03

You're saying endurance athletes supplement with iron? I guess you would know.

This article seems moderately authoritative. TL;DR: Old folks need iron but too much is bad so ask your doctor.

I'll ask.

Edit: It's funny how my ivermectin mania has made me super-inclined to go find sources for information. That wasn't a way of life for me before the pandemic.

[-] thaw4188 | 1 points | Aug 18 2020 23:16:19

low iron is a chronic problem for endurance athletes, red blood cells are constantly destroyed by impact activity and other factors and rbc can only be replaced at 1% per day from the bone marrow so it's a long drawn out process that takes forever to fix

in a marathon for example, the difference between low iron and proper iron levels could mean many minutes in finish time, your muscles literally cannot get enough oxygen because there's not enough transport via RBC

of course too much iron is also bad, very bad since the body has no way to eliminate excess iron on its own like other vitamins and minerals

that's why blood tests have ranges

the sample report on this page demonstrates a low ferritin test

https://www.labtestingapi.com/product/iron-tibc-and-ferritin-panel

[-] TrumpLyftAlles | 1 points | Aug 18 2020 23:26:51

FERRITIN 15 LOW 16-154 ng/mL

OK, I'll keep an eye out for that when I get the results of the blood work.

I was never remotely an endurance athlete, but I did manage to finish two marathons, 4:03 when I was 40 and 5:31 when I was 54. During the first one, I remember figuring out that I had a shot at finishing under 4 hours, urging my legs to run a bit faster, and my legs flat out ignoring me.

Which reminds me, time to walk! :)

[-] TrumpLyftAlles | 1 points | Aug 18 2020 22:56:08

but is ivermectin really a zinc ionosphore?

That surprised me too. Someone on /r/covid19 scolded me for (he said) misstating that it is. I browsed a little, didn't find any authoritative source, e.g. someone who sounded well-informed said ivermectin is an ionophore in a response to a decent blog -- not good enough.

[-] Murky-Lengthiness | 1 points | Jul 13 2020 09:56:11

Thank you! It’s to include the illustrations

[-] Murky-Lengthiness | 1 points | Jul 13 2020 10:00:57

Please feel free to share!!! By the way, until today, Dr. Covid has treated 3909 patients successfully.

[-] nakedrickjames | 3 points | Jul 13 2020 18:34:01

Dr. Covid? That name sounds incredibly suspicious...

[-] Murky-Lengthiness | 1 points | Jul 14 2020 05:21:22

It’s obviously a nickname to protect him or herself from prosecution. Remember the French doctor that when from “hero of France” to “rabid dog” in a few weeks?

[-] Z3rul | 1 points | Jul 14 2020 02:27:33

Dr.Covid? really?

[-] Murky-Lengthiness | 1 points | Jul 14 2020 05:22:52

See above

[-] Murky-Lengthiness | 1 points | Jul 14 2020 05:21:48

.

[-] Murky-Lengthiness | 1 points | Jul 15 2020 02:10:08

I bet Zinc Acetate would be the best because it might be fat soluble wink wink

[-] TrumpLyftAlles | 1 points | Aug 18 2020 23:22:07

I posted an article to the sub here which I think weighs against the idea of ivermectin being an ionophore. Check the link and the paper and let me know your opinion.

Do we really care? Doxacycline is a zinc ionophore. Just add zinc to the Bangladesh pair of ivermectin and doxycycline.

[-] pmcd2 | 2 points | Nov 02 2020 09:26:11

Do you have a reference discussing doxycycline as a zinc ionophore?

[-] TrumpLyftAlles | 1 points | Nov 02 2020 09:44:35

https://www.medrxiv.org/content/10.1101/2020.05.11.20098525v1

[Doxycycline can] act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication.

The full quote:

Doxycycline has been selected based on its ability to: 1) inhibit metalloproteinases (MMPs), implicated in initial viral entry into the cell as well as in acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infection [13, 16]; 2) potential to inhibit Papain-like proteinase (PLpro) responsible for proteolytic cleavage of the replicase polyprotein to release non-structural proteins 1, 2 & 3 (Nsp1, Nsp2 and Nsp3) all essential for viral replication. [19]; 3) potential to inhibit 3C-like main protease (3CLpro) or Nsp5 which is cleaved from the polyproteins causes further cleavage of Nsp4-16 and mediates maturation of Nsps which is essential in the virus lifecycle. [19]; 4) act as an ionophore help transport Zinc intracellularly, increasing cellular concentrations of Zinc to inhibit viral replication. [6, 15]; 5) inhibit Nf-kB which may lower inflammatory response to COVID-19 infection, and lower risk of viral entry due to decreasing DPP4 cell surface receptor. [20, 21]; 6) inhibits (specifically low-dose doxycycline) expression of CD147/EMMPRIN that may be necessary for SARS-CoV-2 entry into T lymphocytes [22, 23].