Covid-19 News

New Japanese Research.. Todai.

Covid-19virus blocks natural human interferon (IFN)

https://www.biorxiv.org/conten…11.088179v1.full.pdf+html

ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist(blocker)
SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV
The anti-IFN activity of ORF3b depends on the length of its C-terminus
An ORF3b with increased IFN antagonism was isolated from two severe COVID49 19 cases

Interferon is a crucial weapon in the human antiviral immune response

https://www.karger.com/Article/FullText/350536

Quote from Shane D.

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-California "urged" nursing homes to accept the infected, and incentivized them by giving $1000 for every patient they accepted.

-Illinois reported >40% of their deaths were in nursing homes.

-Michigan saw a spike in deaths after 24 positive patients transferred to area nursing homes

- 69% of Pennsylvania deaths are in nursing homes, with the most recent data putting that now at 80%

-in March New Jersey ordered nursing homes to accept positive patients. >50% of their deaths from nursing homes

-in March, Gov Cuomo "ordered nursing homes to take in virus positive patients"

In sharp contrast, Florida protected their nursing homes early, and as a result saved many lives: "No Sunshine State patient can be discharged from a hospital into a nursing home without a negative test result. Florida hospitals had already refused to send coronavirus-positive patients back; the new rule means even those who show no symptoms must be tested and confirmed negative."

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It pains me to see such high level criminality and to understand that so many board members here (and ergo most of the population) is in the dark. Before someone has a conniption, I don't believe that every person in this system knows what they are party to.

It is widespread, even the Harvard Chan Public Health team is engaged in disinformation campaigns against HCQ. We have scientists being paid as lobbyists. My guess is "they" employ thousands of people to socially engineer outcomes. To call it oppression would be almost an understatement.

"This study has several limitations. First, this was an observational retrospective analysis that could be impacted by confounding variables. This is well demonstrated by the analyses adjusting for the difference in timing between the patients who did not receive zinc and those who did. In addition, we only looked at patients taking hydroxychloroquine and azithromycin. We do not know whether the observed added benefit of zinc sulfate to hydroxychloroquine and azithromycin on mortality would have been seen in patients who took zinc sulfate alone or in combination with just one of those medications. We also do not have data on the time at which the patients included in the study initiated therapy with hydroxychloroquine, azithromycin, and zinc. Those drugs would have been started at the same time as a combination therapy, but the point in clinical disease at which patients received those medications could have differed between our two groups. Finally, the cohorts were identified based on medications ordered rather than confirmed administration, which may bias findings towards favoring equipoise between the two groups. In light of these limitations, this study should not be used to guide clinical practice. Rather, our observations support the initiation of future randomized clinical trials investigating zinc sulfate against COVID-19."

https://www.medrxiv.org/conten…05.02.20080036v1.full.pdf

Much more interesting than most in vitro drug data

CALU-3 are human lung cancer cells

https://www.biorxiv.org/conten…12.090035v1.full.pdf+html

To interpret these outstanding Nafamostat results:

Plasma levels of NM in healthy volunteers following the administration of 10, 20, and40 mg by a single intravenous drip infusion for 90 min were 10-20, 30-60, and 70-90ng/ml, respectively (5). Plasma levels obtained in a study of multiple doses of 10 and 20mg administered daily for 90 min for 3 days resembled those observed in the single-dosestudy (5). No laboratory test abnormalities were observed.

So we have a conversion job: uM to ng/ml

uM is actually uMol/l.

So to get ng/ml we need to multiply by 1000 X MW ( uMol -> ng) and divide by 1000 (1/l -> 1/ml). So just multiply by MW (molecular weight) (in g/Mol).

The molecular weight of NM? From here p52

Nafamostat mesilate NH2
(6-amino-2-naphthyl p-guanidinobenzoate
dimethanesulfonate, FUT-175)
C19H17N502.2CH403S; Mol wt 539.58

So IC50 = 1.18 ng/ml

That is 15X lower than the typical plasma level of the drug in the lowest experimentally administered one-off dose in humans from the above safety study (10mg IV over 90 min).

NB - 10mg is around 0.15mg/kg

getting this another way:

Clinical trials to evaluate the therapeutic efficacy of NM in patients with DIC have been
performed in Japan (59,63). A well-controlled multicenter study designed to evaluate the
efficacy and safety of NM in DIC as compared with heparin was performed at 57 hospitals
(59). Efficacy was evaluated according to the improvement in clinical manifestations and
in hemostatic parameters that was observed in 56.7% of the patients with DIC who were
administered a continuous infusion of NM (0.2 mg/kg/hr). This was compared with an
efficacy of 47.4% in such patients administered heparin, 10 U/kg/hr intravenously. Although the overall efficacy of NM did not differ significantly from that of heparin,
significantly higher efficacy rates were obtained with NM in nonleukemic patient vs.
those with other malignant tumors (85.7% vs. 30.0%, p < 0.05 by U-test) (59). These
patients developed bleeding complications on heparin, while none did so on NM. The
authors concluded that NM might be an effective alternative to heparin for treating DIC.
By a continuous infusion, NM (0.1 mglkglhr) was effective in treating 75% of patients
with DIC (63). At a dose of 0.2 mglkglhr NM was effective in treating 70% of the
patients. NM was thus as useful as heparin in treating patients with DIC.

0.2 mg/kg/hour continuous looks like a typical clinical dosage. Or a total of 14mg/hour a cross-check for the dosages above.

So the in vitro IC50 levels - according to the plasma tests on healthy volunteers given an IV dose over 90 minutes - really are 15 X lower than the plasma levels

from a low typical continuous dose.

That is very very good news - if these CALU-3 cell tests prove to hold true for in vivo human virus reproduction.

STRONG caution - CALU-3 are human lung cancer cells and therefore not identical to normal tissue.

Respiratory syncytial virus (RSV) replication is primarily limited to the upper respiratory tract epithelium and primary, differentiated normal human bronchial epithelial cells (NHBE) have, therefore, been considered a good system for in vitro analysis of lung tissue response to respiratory virus infection and virus-host interactions. However, NHBE cells are expensive, difficult to culture, and vary with the source patient. An alternate approach is to use a continuous cell line that has features of bronchial epithelial cells such as Calu-3, an epithelial cell line derived from human lung adenocarcinoma, as an in vitro model of respiratory virus infection. The results show that Calu-3 fully polarize when grown on permeable supports as liquid-covered cultures. Polarized Calu-3 are susceptible to RSV infection and release infectious virus primarily from the apical surface, consistent with studies in NHBE cells. The data demonstrate that polarized Calu-3 may serve as a useful in vitro model to study host responses to RSV infection.

There is a Nafamostat RCT but it will take quite some time.

And here is a summary of the Nafamostat stuff:

https://www.eurekalert.org/pub…020-03/tiom-nie032420.php

And here is press news of upcoming fast track UK tests and hospital use:

https://www.express.co.uk/news…avirus-drug-uk-scientists

Looks to me a better candidate for wonder-drug than HCQ. Not that it may not fall by the hurdle of real clinical testing - but it has not yet fallen!

I know a physician group that want to build a Covid site.

Their website has bare bones content (nothing controversial), but this morning I discovered some corporate firewalls are blocking it.

A way of censuring the internet. You will note (if you can see the site) that there isn't even anything really on there!

Can a few people let me know if you can see it (and the country/state you are in?)

https://covid-truth.com

Just a little worrying that in the Gordon et al Nature paper neither camostat not nafamostat showed any activity against the virus at all. I'll stick with HCQ for now as the most potent effective agent, with the rest of Anti Bat. Nice to see other anti malarials such as mefloquine are effective too as I surmised earlier probably underlying the Covid resistance in malarial regions. Still no general acceptance of this hypothesis which is staring epidemiologists in the face. If this was established then I'm sure we would have Anti Bat rolled out worldwide by now as a mass fever treatment and save many, many lives. It isn't going back to normal unless we have effective antivirals available to every citizen to be taken at the first sign of infection, fever or cough, in the way Zelenko has been prescribing to his so called non representative youthful congregation.

So who will be the heroes in the end? I'd put my money on Zelenko and Raoult because they have no vested pharma interest or political reason for being correct. Apart from these two scoundrels everybody else does.

Quote from Navid

I know a physician group that want to build a Covid site.

Their website has bare bones content (nothing controversial), but this morning I discovered some corporate firewalls are blocking it.

A way of censuring the internet. You will note (if you can see the site) that there isn't even anything really on there!

Can a few people let me know if you can see it (and the country/state you are in?)

https://covid-truth.com

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Mcaffee (always the first to block) has blocked it due to phishing:

This is an automatic process.

It is a 3-5 day easy process to request blacklist removal - if you have got rid of the offending behaviour - in this case links to known phishing pages.

McAffee quite often has false positives, but the blacklisting can easily be cleared.

So that's the problem all along if the biochemistry doesn't check out you have to suspect the pharma which is pushing one of its patented drugs. I agree with Wyttenbach this is a can of worms, with different companies coming up with their own expensive wonder drug which even fool our resident sceptic THHuxleynew. Blind you with biochemical pseudoscience elaborating on phosphatase actions which may or may not exist in reality or be relevant. Stick to Anti Bat plus the herbals, supplements and vitamins we suggested before. Avigan can be used instead of Remdesivir as we proposed before, given orally as a precursor with essentially the same effect of blocking viral RNA polymerase. That's clever, and could be replicated by other pyramidine or purine analogues if the drug companies like Gilead want to do something useful with their time rather than pushing their patented Remdesivir. Which nobody can afford.

small but interesting study

Male coronavirus patients with low testosterone levels are MORE likely to die from COVID-19, German hospital finds

https://www.dailymail.co.uk/sc…-likely-die-COVID-19.html

"German hospital assessed the hormone levels of 45 COVID-19 patients in ICUFound that the vast majority of men admitted had low testosterone levels Testosterone may be able to stop the body's immune system from going haywire Low levels of the sex hormone are unable to regulate the body's immune response, leading to a 'cytokine storm' which can be fatal "

Quote from Shane D.

Who would have thought 3 months ago that possibly one of the best candidates for taming the virus would be suppressed and ridiculed, simply because the big bad orangeman was hopeful it "could be a game changer"?

Shane, that is blatently biased / political.

There is absoluytely NO EVIDENCE that anyone is discriminating against HCQ.

By far the largest number of trials - old and new - are for HCQ. The evidence from high quality trials is mixed to say the least. Nevertheless HCQ is being used in many places. And no-one I can see is ridiculing it other than politicians - you should ignore what all politicians say. The doctors do (I think US establishment got pushed a bit pro-HCQ by Trumps edicts but not a lot).

Now - what would you want done for HCQ that is not being done? The RCT evidence just is not there yet to recommend it - as you well know.

THH

Quote from Dr Richard

So that's the problem all along if the biochemistry doesn't check out you have to suspect the pharma which is pushing one of its patented drugs. I agree with Wyttenbach this is a can of worms, with different companies coming up with their own expensive wonder drug which even fool our resident sceptic THHuxleynew. Blind you with biochemical pseudoscience elaborating on phosphatase actions which may or may not exist in reality or be relevant. Stick to Anti Bat plus the herbals, supplements and vitamins we suggested before. Avigan can be used instead of Remdesivir as we proposed before, given orally as a precursor with essentially the same effect of blocking viral RNA polymerase. That's clever, and could be replicated by other pyramidine or purine analogues if the drug companies like Gilead want to do something useful with their time rather than pushing their patented Remdesivir. Which nobody can afford.

So let us have some clarity?

I agree the evidence FOR Nafamostat is pretty small, but there is plausible mechanism and stunningly good in vitro activity on human lung cells.

You are quoting as evidence against Gordon et al

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

Just as clinical trials would outweigh the in vitro activity results, so in vitro activity results, when combined with known dosage levels, outweigh this evidence against. I'm not even sure it is evidence against! And it rests on molecular docking studies against a whole load of vital relevant proteins.

Maybe somone who understands it (I don't) could explain how string negative evidence from this - and also find the list of all the drugs that it tested for activity against these targets?

THH

Quote from Shane D.

Yes, HCQ is not proven yet, and even the small portion of the massive media industry conservatives own (Fox News) has been careful to say that.

The drug was “a game changer” in the fight against the coronavirus, [Ingraham] declared. She booked recovered patients to describe their “miracle turnaround” — “like Lazarus, up from the grave”. Anyone who questioned the drug’s efficacy, she said, was “in total denial.”

“I love everybody, love the medical profession,” [Ingraham] said on April 3, after listing off public health experts who questioned the cure. “But they want a double-blind controlled study on whether the sky is blue.”

Quote from THHuxleynew

There is absoluytely NO EVIDENCE that anyone is discriminating against HCQ.

Really?

Wants Trump tried for crimes against humanity for suggesting HCQ.

https://www.nbcnews.com/news/n…against-humanity-n1178501

Adam Schiff - US congressman leading the failed impeachment fiasco. Certainly, he is painting the picture that HCQ is linked to Trump and therefore not to be used.

An article detailing the obvious political discrimination (for and against) HCQ.

http://bostonreview.net/scienc…chloroquine-and-political

This article, concluding with : https://www.washingtonpost.com…roquine-its-consequences/

"In particular, Trump’s incorrect comments on the drugs and his role in advocating for their use, based on minimal and flimsy evidence, sets a bad example. His advocacy for this unproven treatment provides potentially false hope and has led to shortages for people who rely on the drugs. The president earns Four Pinocchios."

Is blatantly tying HCQ to Trump in a clearly "veiled way" to discredit it's use. Note examples in the article such as stating a "rush" on HCQ caused by Trump's remarks have caused shortages that deprive lupus and arthritis patients of their much needed medicine, yet later stating that HCQ is dangerous and life threatening.

Your statement of "NO EVIDENCE" (in caps mind you) is very telling of your bias. We all know you are quite intelligently capable of recognizing what is being spread around the news and political arena. For you to make this statement is about as ludicrous as the ones made by Rossi believer's trying to defend their continued support of Rossi.

A member of a political party calling for crimes against humanity to be charged for the use of HCQ is "NO EVIDENCE" of discrimination! Really?

I am not sure how effective HCQ is. The same with the others such as Remdesivir, Yet for some reason, I do not see you posting "WARNINGS" against these other unproven, untested, to RTC drugs as you do HCQ. While you do not come out and say HCQ is an absolute failure, your own weighted postings clearly indicate that your are biased against it's use. It appears simply because of who is "encouraging" it's use. No bias against Remdesivir for it's being tauted, but HCQ is a political issue now..... and yes, plenty of evidence it is being discriminated against due to that reason alone.

Just like many here claim you are against LENR and you claim you are not. (I actually think you are not against it, but that you just do not believe in it), you claim not to be biased against HCQ, but it appears quite readily by the content of your posts, you are somewhat biased against it because of who supports it, RE: you do not diminish most other possible drugs the same unless they are touted by the "HCQ crowd". Just my opinion of a pattern I see posted.

Quote from Bob#2

Just my opinion of a pattern I see posted.

This type of stirring the pot is what some online posters want. A hornet's nest of argumentation and uncertainty. Smith-Mundt is what you need to know.