The history of the nursing home in Cali that prevented 59 elderly people from getting worse with covid-19 (Cali Colombia 2020-10-23)

[-] TrumpLyftAlles | 4 points | Oct 24 2020 06:52:58

Nice win for ivermectin etc: 59 covid+ elderly patients were treated early with Ivermectin + aspirin + Nitazoxanide. They all recovered.

A publication is coming. Keep your eyes peeled!

Imagine that you are asleep at midnight and a thief enters. The rogue begins to steal, and if he suspects that you are at home, he will enter your room, tie you hand and foot, and gag you so that you will not call the police or put up resistance. Then he will steal at ease.

Something similar happens with the Coronavirus, according to the pharmacologist Óscar Gutiérrez, who explains that the virus invades the cell and uses its mechanisms to reproduce, that is, to create copies of itself. If the virus reaches the nucleus of the cell, it leaves it unable to defend itself, just as in the example of the thief at midnight.

The effect of blocking the import alpha/beta1 transport is preserving the cell's immune function.

But there are low-cost methods that, used on time and within a careful medical protocol, can trip the Coronavirus, make things difficult for it, and give the cell time to defend itself.

This idea, applied, already has a recent success story in the city. It is the San Miguel Geriatric and Elderly Hospital, where an interdisciplinary group met in March to assess the potential risk faced by older adults hospitalized there.

Seeing the terrible news that came from Europe, where developed countries such as Belgium, France and Italy had very high mortality of older adults confined in geriatric centers, because of the Covid, they set off the alarms.

How to prevent the same story from repeating itself in the San Miguel? The first thing they did, according to Dr. Óscar Gutiérrez, was to implement strict biosecurity precautions: visits were suspended, the use of masks, alcohol and constant hand washing became mandatory.

They also classified the 254 patients, with an average age of 79 years, according to risk factors from 1 to 9, with 1 being the most vital and autonomous patients and 9 those with the most comorbidities.

In addition, a special area was adapted for those patients who came to present suspicious symptoms, and another area to give immediate attention to patients who require it.

It was calculated that, if the virus reached San Miguel, at least half of the patients were at risk of dying, so the slogan was: prevent and act quickly in any eventuality, so that none of the older adults had to be referred to an ICU.

Thus, everyone under alert, from the person who washes the floor to the kitchen staff, the patients and the medical staff, the days passed.

The first week of August an employee of the San Miguel reported some mild symptoms. All hospital residents and staff were immediately screened, and close contacts were treated.

59 residents of the nursing home tested positive, and 19 of them were hospitalized within the same center. None required transfer to the ICU or ventilatory support.

Dr. Óscar and his colleagues in the interdisciplinary medical corps made a decision in accordance with the Helsinki declaration of ethics, on unproven interventions in clinical practice. They applied triple treatment to all the patients, not just the 59 who tested positive.

Prophylaxis! But it doesn't say whether any not-yet-infected nursing home residents caught the virus.

And this treatment consisted in prescribing Ivermectin, which used in the early phase of the virus makes it difficult to enter the cell and makes it difficult to act; Aspirin to prevent the formation of blood clots which, due to the Coronavirus, can collapse organs such as the lungs; and Nitazoxanide, an antiparasitic used successfully in other viral diseases, and that, like Ivermectin, sabotages the action of the Coronavirus.

Ivermectin + aspirin + Nitazoxanide

The results of this protocol could not have been better, because despite the advanced age of the patients (including a 102-year-old woman), there were zero deaths. All patients, treated on time with this method and inexpensive, since it cost between $ 13 and $ 20 per person, recovered.

Wow, age 102 saved. Drugs were $13 - $20 per patient. Are those in Colombian pesos? The converter says the equivalent in US dollars is $0.00 to $0.01. That doesn't sound right.

Gutiérrez, who will share the scientific details of this report in an international publication in the next few days, argues that this success story presented in Cali, among older adults, can also serve as inspiration for many more centers, cities and regions, and invites not neglect essential biosecurity care. Alcohol, soap, mask and distancing.

Report coming!

Teamwork

- Success Story Héctor Cortés, director of the Hospital San Miguel; Raúl Corral, Óscar Gutiérrez, Alejandro Varela, Bertha López, Mauricio Ocampo, César Rueda, Francisco Muñoz, Diana Castillo, Lizeth Londoño, Alberto Concha, are part of the interdisciplinary team that launched the measures, aligned with the MinSalud protocols.

The biosafety measures and the early therapeutic approach, led by Dr. Héctor Cortés and his team, prevented the progress of the infection towards major complications, and the hospitalization of greater complexity in this vulnerable population.

[-] saitchouette | 3 points | Oct 24 2020 07:31:51

From Paola Guevera's article

according to the pharmacologist Óscar Gutiérrez, who explains that the virus invades the cell and uses its mechanisms to reproduce, that is, to create copies of itself. If the virus reaches the nucleus of the cell, it leaves it unable to defend itself

TrumpLyftAlles

The effect of blocking the import alpha/beta1 transport is preserving the cell's immune function.

I agree, in theory. My (layperson) understanding is that preventing the virus from sending nucleocapsid proteins (NPs) into the nucleus has the potential to be an effective treatment. That is because those NPs have the potential to stop the cell's innate immune response. I gather the NPs would otherwise infiltrate the nucleus by binding to the importins which you mention. So it's great if ivermectin can stop that happening and, thereby, stop the SARS-CoV-2 NPs from entering the nucleus. That way, the cell has a fighting chance at beating SARS-CoV-2. (Not sure if I've described the process correctly.)

However, all this rests on the assumption that SARS-CoV-2 NPs go into the nucleus. Has it been established that they do go into the nucleus? Or that they don't?

If the NPs don't go into the nucleus, is there another benefit to preventing NPs from binding with importins? There may well be some other antiviral benefit that I just don't know about (or would struggle to get).

I agree with you, and others, that there's an overwhelming correlation between the administering of ivermectin and efficacious treatment of COVID-19 (by way of inhibit viral replication). But so many questions as to the means by which this happens.

[-] massimaux | 3 points | Oct 24 2020 16:04:47

I remember Dr. Wagstaff's reply to u/TrumpLyftAlles's query. One part was especially interesting to me:

Our Vero line is permissible to SARS-CoV-2 infection so it does express ACE2 to some degree, however it is not an ideal cell line for examining ivermectin as it does not express interferon alpha or beta, which is fundamentally the process by which I think ivermectin works in this instance (my current hypothesis is that SARS-Cov-2 inhibits interferon production by blocking imp a/b and ivermectin alleviates this).

Before making the point, let's recall what happens normally in an infected cell. Dr. John Campbell gave a nice lecture on interferon production. Normally, interferons are produced when cells’ virus alarms are activated. Interferons flood into the infected area, signal uninfected cells to raise their defenses, and help kill infected cells.

If Dr. Wagstaff's hypothesis is correct, then, ivermectin is helping the rogue immune system (in to-be-severe cases) produce interferon as the first line of defense and get rid of the virus in the first few days of infection.

Obviously, in this theory, the key is to produce interferons immediately when the cells get infected and there are at least three ways to achieve this:

A healthy innate immune system would produce interferons by itself immediately and is going to be fine.
A rogue innate immune system would not produce interferons in the first few days and there is big risk of going into cytokine storm. To help the immune system, one would inject interferon into the body and this should be done in the early stage. Interferons will kill off infected cells and it's likely going to be fine.
A rogue innate immune system would not produce interferons in the first few days and there is big risk of going into cytokine storm. To help the immune system, one would take ivermectin, which will prevent the virus from shutting off the alarm and the cells would produce interferon. This should be done in the early stage. Interferons will kill off infected cells and it's likely going to be fine.

Does this make sense or have I got it wrong?

[-] TrumpLyftAlles | 1 points | Oct 24 2020 17:04:01

Sounds good to me! Excellent analysis!

[-] massimaux | 3 points | Oct 24 2020 18:28:47

Thanks. I just located this article, it's too complicated for me to understand but it seems that they do have data proving that SARS-CoV-2 messes with the nuclear interferon signaling:

All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

This FB comment is very informative regarding IVM's role.

If IVM is inhibiting this evil viral action then we are good. :)

[-] TrumpLyftAlles | 2 points | Oct 24 2020 23:37:05

From Facebook (the last quote comes from the posted link):

"SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling"

Interferon signaling is a critical element in the apoptotic mechanism (programmed cell death) of the innate immune system and the balance between innate and cell-mediated immunity. This is likely why #SARSCoV2 is able to replicate so efficiently which necessarily induces cytokine storm as the adaptive immune system goes into overdrive in order to make up for a hamstrung innate response.

Takeaways:
(1) Inoculum is absolutely determinative in outcome
(2) #Ivermectin is more valuable than #HCQ because it binds to nuclear heterodimer importin alpha/beta complex and prevents the virus from gaining access to the cell nucleus. HCQ can't do this.

Read this 👇
"The IFNs (interferons), which are essential for initiating and coordinating a successful antiviral response, function by stimulating the adaptive arm of immunity involving cytotoxic T cells (CTLs), and by inducing a number of intracellular genes that directly prevent virus replication/cytolysis or that facilitate apoptosis."

Host defense, viruses and apoptosis

[-] TrumpLyftAlles | 1 points | Oct 24 2020 23:29:57

I'm not sure this adds anything.

From the article (not Facebook):

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.

And then:

Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus

Proteins with a molecular mass greater than ~45 kDa generally require an NLS (nuclear localization signal) to gain entry into the nucleus via the nuclear envelope-localized NPCs (nuclear pore complexes). NLSs are generally recognized by members of the Imp (importin) superfamily of proteins, NLS recognition commonly being through the Impα adaptor protein within the Impα/β1 heterodimer, or Impβ1 or homologues thereof directly.

In the present study, we investigated the effects of ivermectin treatment on the subcellular localization of numerous NLS-bearing cargo proteins, demonstrating that ivermectin is a potent inhibitor of Impα/β1-dependent transport, with no effect on proteins containing NLSs recognized by alternative nuclear import pathways.

[-] jewelsn24 | 3 points | Oct 25 2020 04:45:55

It has been proven that SarsCov2 enters the nucleus as all viruses enter the nucleus via the cell and cause the nucleus to create more copies of itself instead of more copies of the invaded cell itself. Btw Professor Borody's podcast has been delayed by Trialsite and they will be updating us with the revised date soon. Thanks for this great article. I can't wait to hear more about it in the coming week.

[-] Haitchpeasauce | 3 points | Oct 25 2020 10:40:44

SARS-CoV-2 replicates in the cytoplasm of the cell, outside the nucleus. It sends an accessory protein into the nucleus which disrupts interferon response. Thanks for the update about the interview.

[-] jewelsn24 | 3 points | Oct 25 2020 10:57:53

Thank you for this very interesting information I know the new evidence says that it probably interferes with the interferon response which is responsible for the initial innate immune response. I didn't know about it replicating in the cytoplasm and sending an accessory protein into the nucleus disrupting the interferon response this way. Morbidly fascinating.

[-] Haitchpeasauce | 3 points | Oct 25 2020 11:07:49

Yeah it's that protein that Ivermectin is theorised to prevent from being transported into the nucleus. Absolutely fascinating virus indeed.

[-] massimaux | 1 points | Oct 25 2020 15:53:39

Do you know by chance what's really happening with Borody's trial in aged care homes in Victoria? 27 days ago, he said on a podcast that he was going to come up with "joint announcement and statement probably in a couple of weeks" but nothing yet. I'm worried that the therapy was not effective enough. Hopefully, it's not the case.

[-] jewelsn24 | 3 points | Oct 25 2020 21:34:43

I know that Dr Sabine Hazan his partner just recently applied for the trademark registration name "Ziverdox" which is the name of the combination of drugs Ivermectin, Doxycycline, Zinc on October 12th. I also heard one of the Chief Medical Officers say that they hadn't had any cases in the nursing homes in Melbourne for a few weeks now and zero deaths. Trial site said he had a conflict with his scheduling dates so they had to delay the podcast. That's all I can tell you. Looks promising as Melbourne just reported 0 cases and 0 deaths from Coronavirus today so we shall see. Cross fingers. I think he might be doing the media rounds this week or next.

[-] massimaux | 3 points | Oct 25 2020 23:09:13

Thank you for the update.

[-] Haitchpeasauce | 1 points | Oct 26 2020 06:01:31

I noticed a sharp decline in cases in Victoria and have wondered if it's connected to the triple therapy trials. Eagerly awaiting Borody's interview with TrialSiteNews.

[-] TrumpLyftAlles | 1 points | Oct 24 2020 07:42:21

all this rests on the assumption that SARS-CoV-2 NPs go into the nucleus. Has it been established that they do go into the nucleus? Or that they don't?

I don't know.

However, this paper suggests that there are agents other than nucleocapsid proteins, maybe. I don't understand this stuff.

However, whether and how SARS-CoV-2 antagonizes IFN production and signaling is not clear.

After phosphorylation and dimerization, IRF3/7 translocates to the nucleus to activate the expression of IFN-α/β.

It's late and I'm tired. Can you look at the paper and try to figure out what it implies?

Also:

Pre-covid19 papers about SARS turned up by googling

"nucleocapsid proteins" covid-19 nucleus

https://www.frontiersin.org/articles/10.3389/fmicb.2015.00553/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106238/

https://jvi.asm.org/content/75/19/9345

https://europepmc.org/article/pmc/pmc7176212

These are covid19-related:

https://link.springer.com/article/10.1007/s00018-020-03603-x

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310621/

[-] saitchouette | 1 points | Oct 24 2020 07:49:03

I'll try to have a look tonight. Ah yep must be terribly late Stateside. Early evening on the Australian east coast.

[-] TrumpLyftAlles | 1 points | Oct 24 2020 23:19:57

At around 20:00 the video that Dr. Marik released today (2020-10-24):

So how does ivamectin work as an antiviral? so this is one of the theories postulated by these authors and supported by very good scientific data. So what happens, and this is a really truly mysterious thing, is that sarkov2 protein and in this case it seems to be the nuclear capsid protein binds to what are called important proteins important alpha and beta and this allows these proteins to go through the nuclear pore and into the nucleus. So proteins can't just get into the nucleus to get into the nucleus it has to go through this nuclear pore and it's achieved through these importance the nuclear capsule protein binds to these importance and gets imported into the nucleus where it causes havoc.

[-] jewelsn24 | 3 points | Oct 25 2020 11:10:30

I honestly think that this will end up being one of the gold standard treatments for it along with the Doxycycline/zinc combo and of course a vaccine.

[-] jewelsn24 | 1 points | Oct 25 2020 23:10:23

No problems. Here's hoping.

[-] jewelsn24 | 1 points | Oct 26 2020 06:24:38

Yes I agree. I think he might be doing the media rounds this week. Hope so.