Quote from JedRothwell

This statement makes no sense. Merck, the Big Pharma that makes the ivermectin, says it does not work! It discourages the use of this drug. Why would this company tell people not to use its own product?

Merck wants to sell a new drug with 1000x $$$$$. But this is may be to difficult for you to understand.

Quote from JedRothwell

People are NOT dying from the vaccine. There has not been a single instance of that.

So far we had about 500 Pfizer vaccine induced deaths. All documented in the CDC database. Norway stopped the use of the Pfizer vaccine for people aged > 80 after more than 20 deaths occurred.

But you prefer to live in a fantasy world.

SARS-CoV-2 with Genomic Deletions Escapes an Antibody

Researchers identify deletions in the N-terminal domain of the spike protein that allow the coronavirus to avoid antibody neutralization and that may contribute to the emergence of new variants

https://news.google.com/articl…=en-US&gl=US&ceid=US%3Aen

When SARS-CoV-2, the virus behind the COVID-19 pandemic, first emerged, scientists expected it to evolve slowly because the virus copies its big RNA genome with a polymerase that also corrects errors, thus minimizing the chance for certain types of mutations. This enzyme functionality isn’t present in other RNA viruses such as influenza and HIV, which accumulate single nucleotide polymorphisms, where one nucleotide is substituted for another, much more quickly than SARS-CoV-2 does.

This genomic stability was thought to be good news for vaccine design, but it’s become apparent in recent months, with the emergence of B.1.1.7, B.1.351, and other variants, that SARS-CoV-2 is mutable—and might put up a fight against neutralizing antibodies that go after the spike protein of the virus. In a study posted as a preprint in November and published February 3 in Science, researchers showed that SARS-CoV-2 tends to delete portions of RNA that encode the N-terminal domain (NTD) of the spike, a mutation that its proofreader can’t detect. These findings and those of other groups offer an explanation for how new SARS-CoV-2 variants arise and escape antibody recognition by the host immune system.

Deletion “represents a way to rapidly alter an entire stretch of amino acids and more rapidly alter the structures that those amino acids are contributing to,” says coauthor Kevin McCarthy, a virologist at the University of Pittsburgh. These mutations “could accelerate [SARS-CoV-2] evolution and then complement mutations that it’s already making.”

The project started when two physicians at the University of Pittsburgh Medical Center contacted Paul Duprex, a virologist and the director of the Center for Vaccine Research at Pitt. The doctors had an immunocompromised cancer patient who passed away after a SARS-CoV-2 infection that lasted 74 days and did not respond to common treatments, including Remdesivir and dexamethasone. So Duprex and his team took a look at the viral genome to see if they could figure out why the infection lasted so long.

From samples aspirated from the patient’s trachea 72 days after the initial COVID-19 diagnosis, the researchers isolated viral RNA from several SARS-CoV-2 variants, which likely evolved from one initial infection during the long illness, and sequenced the S gene, which encodes the spike protein. They found two variants that contained different three-nucleotide deletions in the NTD of the spike protein.

What makes new variants of SARS-CoV-2 concerning is not where they come from, but the mutations they contain

https://blogs.bmj.com/bmj/2021…e-mutations-they-contain/

In the past three months global attention has turned to the discovery and relative global health risks of new variants of the SARS-CoV-2 virus. News today suggests that a new covid variant, B1525, has been identified in the UK. In December, the discovery of what has become popularly known as the “Kent variant,” or to give it’s proper name B.1.1.7, led to a virus sweeping across the United Kingdom and dominating infections due to an increase in transmissibility. This was followed by the “South African” variant B.1.351 which contains a mutation now being reported to reduce the efficacy of the ChAdOx vaccine to the extent that South Africa are removing the vaccine from their vaccination programme. The “Brazil” variant P.1 is also spreading to multiple countries with worries about its propensity for causing re-infections, given its emergence in a place that may have already hit herd immunity in the first wave.

The world now seems obsessed with SARS-CoV-2 variants and designating them with a place of origin. This is an unfortunate stigma that should be avoided at all costs given that where a virus is first detected is not necessarily where it originated. Lest we forget, Spanish Flu (the 1918 Influenza pandemic) had absolutely no connection to Spain.

The obsession with variants is now becoming as contagious as the virus, and unfortunately is also provoking similar knee jerk reactions. The discovery of the B.1.351 variant in the UK has led to a mass scale targeted testing (surge testing?) and sequencing regimen in affected areas in an attempt to control its spread. This is due to a press release statement that the ChAdOx vaccine did not protect against mild and moderate covid-19 symptoms in a very small South African study of young adults. While prudence and quick action should always be advised in matters of Covid, it is also worth remembering that none of the data are published and so a significant supposition is being made on the ability of the Oxford AstraZeneca vaccine to control B.1.351 cases. Borders are now being closed in efforts to prevent numerous introductions of new variants of concern into the UK and other countries, but will this truly protect us from new SARS-CoV-2 variants?

What makes the variants of concern concerning is not where they come from, but the mutations they contain. The B.1.1.7 virus is characterised by a deletion in the spike protein and a mutation at N501Y which enhances its transmissibility, as well as a potentially important mutation in the furin cleavage site. These mutations are found on a background of an unusually high number of other mutations making B.1.1.7 distinct. In the case of B.1.351 the key mutation which makes it a threat to vaccine efficacy is the E484K mutation in the spike protein, also seen in P.1. However, it is incredibly naïve to think that these mutations of concern are restricted to singular geographically defined viral lineages.

What has driven the emergence of these phenotypically important mutations are significant selection pressures. In the case of B.1.1.7 random mutations conferring an increase in transmissibility led to an increase in fitness of the virus which was rapidly selected for and became dominant in the UK. In the case of B.1.351 it may be that selection is for a random mutation allowing some form of enhanced escape from immune pressure and onward transmission, generating a fitness advantage—although evidence remains weak for this. The key salient point here is that these selection pressures are not geographically specific. The virus is encountering similar selection pressures wherever it is transmitting and has relatively high prevalence, meaning that the selection for random mutations that can confer a fitness advantage can happen anywhere, and at any time. This is now being seen with the emergence of the E484K mutation in the B.1.1.7 virus variant, meaning that the “Kent” variant now has the important “South Africa” mutation.

Another Potentially Immunity-Evading SARS-CoV-2 Variant Detected

B.1.525 shares a mutation with the B.1.351 variant first detected in South Africa that seems to allow the virus to dodge the immune system

https://news.google.com/articl…=en-US&gl=US&ceid=US%3Aen

Researchers in the UK have identified a new SARS-CoV-2 variant with mutations that could allow it to evade immunity-conferring neutralizing antibodies.

Known as B.1.525, the variant was first detected in the UK and Nigeria in December. It’s since been found in 11 other countries, including Denmark, the US, and Australia.

Quote from Fm1

The world now seems obsessed with SARS-CoV-2 variants and designating them with a place of origin. This is an unfortunate stigma that should be avoided at all costs given that where a virus is first detected is not necessarily where it originated. Lest we forget, Spanish Flu (the 1918 Influenza pandemic) had absolutely no connection to Spain.

It was openly reported in Spain because Spain was not fighting WWI, so there was no wartime censorship there. The French, British and Germans downplayed the extent of the epidemic, because it was affecting their ability to wage war. So Americans thought the epicenter was in Spain.

Quote from Fm1

The obsession with variants is now becoming as contagious as the virus, and unfortunately is also provoking similar knee jerk reactions. The discovery of the B.1.351 variant in the UK has led to a mass scale targeted testing (surge testing?) and sequencing regimen in affected areas in an attempt to control its spread.

Yes but . . . but . . . All variants have to originate somewhere, in one patient. If you can identify a location with patients who have a dangerous variant that has not yet spread to other places, you might be able to take steps to reduce the spread. Or if it has not yet spread far, and there are not many patients yet, you can begin emergency preparations such as modifying an mRNA vaccine for use in that one area. If only the Chinese had identified and aggressively treated the first cases of COVID-19, it might have been stopped in Wuhan before infecting the whole world.

Here is a melancholy statistic. It shows the ~6 week lag between infection and death. The data from Georgia is looking good in every parameter but one: "Newly reported deaths by day" has not declined. Infections, hospitalizations, Percent testing positive, and the effective reproduction number Rt are all down. No doubt deaths will soon decline.

https://www.ajc.com/news/coron…d/jvoLBozRtBSVSNQDDAuZxH/

Differential roles of RIG-I-like receptors in SARS-CoV-2 infection

https://www.biorxiv.org/conten…/2021.02.10.430677v1.full

Abstract

The retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are the major viral RNA sensors that are essential for activation of antiviral immune responses. However, their roles in severe acute respiratory syndrome (SARS)-causing coronavirus (CoV) infection are largely unknown. Herein we investigate their functions in human epithelial cells, the primary and initial target of SARS-CoV-2, and the first line of host defense. A deficiency in MDA5 (MDA5−/−), RIG-I or mitochondrial antiviral signaling protein (MAVS) greatly enhanced viral replication. Expression of the type I/III interferons (IFN) was upregulated following infection in wild-type cells, while this upregulation was severely abolished in MDA5−/− and MAVS−/−, but not in RIG-I−/− cells. Of note, ACE2 expression was ~2.5 fold higher in RIG-I−/− than WT cells. These data demonstrate a dominant role of MDA5 in activating the type I/III IFN response to SARS-CoV-2, and an IFN-independent anti-SARS-CoV-2 role of RIG-I.

Vitamin D Activation and Function in Human Corneal Epithelial Cells During TLR-Induced Inflammation

https://pubmed.ncbi.nlm.nih.gov/26641549/

Abstract

Purpose: Vitamin D is recognized to be an important modulator of the immune system. In the eye, studies have shown that deficiencies and genetic differences in vitamin D-related genes have a significant impact on the development of various ocular diseases. Our current study examines the ability of human corneal epithelial cells (HCEC) to activate vitamin D and the effect of vitamin D treatment on antimicrobial peptide production and cytokine modulation during inflammation, with the ultimate goal of using vitamin D therapeutically for corneal inflammation.

Methods: Human corneal epithelial cells were treated with 10-7M vitamin D3 (D3) or 25-hydroxyvitamin D3 (25D3) for 24 hours and 1,25-dihydroxyvitamin D3 (1,25D3) detected by immunoassay. Human cathelicidin (LL-37) expression was examined by RT-PCR, immunoblot, and immunostaining following 1,25D3 treatment and antimicrobial activity of 1,25D3-treated cells was determined. Cells were stimulated with TLR3 agonist polyinosinic-polycytidylic acid (Poly[I:C]) for 24 hours and cytokine levels measured by RT-PCR, ELISA, and Luminex. Immunostaining determined expression of vitamin D receptor (VDR) and retinoic acid inducible gene-1 receptor (RIG-1) as well as NF-κB nuclear translocation.

Results: When treated with inactive vitamin D metabolites, HCEC produced active 1,25D3, leading to enhanced expression of the antimicrobial peptide, LL-37, dependent on VDR. 1,25-D3 decreased the expression of proinflammatory cytokines (IL-1β, IL-6, TNFα, and CCL20) and MMP-9 induced by Poly(I:C) as well as pattern recognition receptor expression (TLR3, RIG-1, MDA5). However, early activation of NF-κB was not affected.

Conclusions: These studies demonstrate the protective ability of vitamin D to attenuate proinflammatory mediators while increasing antimicrobial peptides and antipseudomonas activity in corneal cells, and further our knowledge on the immunomodulatory functions of the hormone.

Quote from JedRothwell

Merck, the Big Pharma that makes the ivermectin, says it does not work! It discourages the use of this drug. Why would this company tell people not to use its own product? If it was only interested in making money, why would it not want people to use the drug? This is contrary to the company's interest.

In a Big Bad Pharma conspiracy theory scenario, Merck would love to sell ivermectin to treat COVID-19. Because it doesn't work! They could sell millions of doses, yet it would not reduce the sales of any other drug they sell, or any other Big Pharma conspirator sells. It is an ideal way to make money. You sell a non-working bogus cure. The patient remains as sick as ever. If you have any actually effective drugs, you sell them as well. Not only that, but Merck has loudly declared ivermectin does not work, so they can't be sued because it fails. They have no risk!

In the dark fantasy world of conspiracy theorists such as Navid, Merck would love to sell this. Here in the real world, companies that engage in that kind of unethical behavior are punished by patients, doctors, regulators and society, so they would be idiots to do that. Say what you like about Big Bad Industry, it is seldom run by idiots. With notable exceptions such as GE in recent years. See the book "Lights Out: Pride, Delusion, and the Fall of General Electric." This book demonstrates that when a company goes off the rails and does stupid things, you can tell. The stock value falls. GE was removed from the Dow Industrial Average. The company goes bankrupt if it does not stop doing stupid things. If Merck and the other Big Pharma companies did the kinds of things Navid accuses them of, they would be destroyed in class action lawsuits.

Exclusive: Two variants have merged into heavily mutated coronavirus

The UK and California variants of coronavirus appear to have combined into a heavily mutated hybrid, sparking concern that we may be entering a new phase of the covid-19 pandemic

https://www.newscientist.com/a…vily-mutated-coronavirus/

Two variants of the SARS-CoV-2 coronavirus that causes covid-19 have combined their genomes to form a heavily mutated hybrid version of the virus. The “recombination” event was discovered in a virus sample in California, provoking warnings that we may be poised to enter a new phase of the pandemic.

The hybrid virus is the result of recombination of the highly transmissible B.1.1.7 variant discovered in the UK and the B.1.429 variant that originated in California and which may be responsible for a recent wave of cases in Los Angeles because it carries a mutation making it resistant to some antibodies.

The recombinant was discovered by Bette Korber at the Los Alamos National Laboratory in New Mexico, who told a meeting organised by the New York Academy of Sciences on 2 February that she had seen “pretty clear” evidence of it in her database of US viral genomes.

If confirmed, the recombinant would be the first to be detected in this pandemic. In December and January, two research groups independently reported that they hadn’t seen any evidence of recombination, even though it has long been expected as it is common in coronaviruses.

Unlike regular mutation, where changes accumulate one at a time, which is how variants such as B.1.1.7 arose, recombination can bring together multiple mutations in one go. Most of the time, these don’t confer any advantage to the virus, but occasionally they do.

Recombination can be of major evolutionary importance, according to François Balloux at University College London. It is considered by many to be how SARS-CoV-2 originated.

Recombination could lead to the emergence of new and even more dangerous variants, although it isn’t yet clear how much of a threat this first recombination event might pose.

Korber has only seen a single recombinant genome among thousands of sequences and it isn’t clear whether the virus is being transmitted from person to person or is just a one-off.

Quote from JedRothwell

There is no need to lead any charge. Any doctor who wants to use ivermectin is free to do so. It is being widely used, even though most experts feel that tests show it does not work.

This statement makes no sense. Merck, the Big Pharma that makes the ivermectin, says it does not work! It discourages the use of this drug. Why would this company tell people not to use its own product? If it was only interested in making money, why would it not want people to use the drug? This is contrary to the company's interest.

Maybe because it's not their "own product" and that there is no money to make given that Merck's patent on ivermectin expired in 1995 and since then Merck donated (i.e. not sold) more than 4 billions doses worldwide? See https://www.merck.com/stories/mectizan/

Or that ivermectin would impact their multi-$100M sales of Mk-7110, MK-4482 and Rebif repurposed for COVID-19 treatment...

Again, here is the science on ivermectin:

https://ivmmeta.com/

I'm still waiting for the first negative study of ivermectin on COVID-19, despite what you continue to claim....

Quote from JedRothwell

, Merck would love to sell ivermectin to treat COVID-19.

No it wouldn't. The only profit would not be Merck's, but small peanuts for generic drug makers ,probably in India.

There is no profitable patent on a 40 yr old drug

https://www.researchgate.net/p…-Developing-Countries.pdf

Plaudits for Merck's past philanthropy with Mectizan.>But.>
Philanthropy dies when IVM competes with a patentable product

and Merck has it's new patentable candidate. MK-7110, hopeful since December

'The U.S. government will pay Merck & Co. $356 million for between 60,000- 100,000 doses of an experimental drug being tested as a treatment of gravely ill patients hospitalized with COVID-19.'

Zannen ne. Some aggravation for Merck. February 9. Get those bribes/wairo ready.

Tokyo Medical Association recommends ivermectin administration to prevent aggravation

https://www.nikkei.com/article/DGXZQOFB25AAL0V20C21A1000000/

Quote from Wyttenbach

...

So far we had about 500 Pfizer vaccine induced deaths. All documented in the CDC database. Norway stopped the use of the Pfizer vaccine for people aged > 80 after more than 20 deaths occurred.

But you prefer to live in a fantasy world.

There are many deaths reported and recorded, but what I can read below says something different... (from today’s CDC COVID vaccination tracker data base...)

https://www.cdc.gov/coronaviru…afety/adverse-events.html

„Over 52 million doses of COVID-19 vaccines were administered in the United States from December 14, 2020, through February 14, 2021. During this time, VAERS received 934 reports of death* (0.0018%) among people who received a COVID-19 vaccine. CDC and FDA physicians review each case report of death as soon as notified and CDC requests medical records to further assess reports. A review of available clinical information including death certificates, autopsy, and medical records findings revealed no link with vaccination. CDC and FDA will continue to investigate reports of adverse events, including deaths, reported to VAERS„

I know that is the official statement, but maybe there are other sources?

Quote from RobertBryant

'The U.S. government will pay Merck & Co. $356 million for between 60,000- 100,000 doses of an experimental drug being tested as a treatment of gravely ill patients hospitalized with COVID-19.'

This is how FM/R mafia members inside deep state finance their friends with public - taxpayers money. The EU did buy Gilead crap Remdesivir they now have to run through the toilet -- or may wait for some Ebola to happen...

The Swiss FM/R mafia did buy vaccines for 3x the population albeit here at most 50% want to have it ever...

Quote from JedRothwell

In a Big Bad Pharma conspiracy theory scenario, Merck would love to sell ivermectin to treat COVID-19.

You seem to know nothing about big pharma business!

Looks like you have to defend your buddies.

Study shows how SARS-CoV-2 uses an immune system defense for replication

https://news.google.com/articl…=en-US&gl=US&ceid=US%3Aen

The immune system actually wants to fight SARS-CoV-2 with antiviral signaling molecules. But a research team from Charité and MDC has now shown how such a signaling molecule can promote the replication of the virus. The results have been published in the journal EMBO Molecular Medicine.

Most people infected with SARS-CoV-2 are able to recover from the disease at home - even if they might experience very stressful disease progressions. Some have no symptoms at all. But about ten percent of those affected become so severely ill that they have to be treated in a hospital.

The assumption that a weak immune system is behind a severe progression is short-sighted. Especially with critical progressions, the immune system works under intense pressure but does not manage to control the virus.

A Berlin research group has now observed how SARS-CoV-2 uses an immune system defense mechanism to increasingly hijack the body's mucous membrane cells and multiply there. Their study has just appeared in the journal EMBO Molecular Medicine.

"This may give us part of the explanation as to why the immune system has difficulty regulating or even defeating the infection in some people," says Dr. Julian Heuberger, a scientist at the Division of Hepatology and Gastroenterology in Charité - Universitätsmedizin Berlin's Medical Department.

He is the first author of the study and a member of an Emmy Noether Research Group led by PD Dr. Michael Sigal at Charité and the Berlin Institute for Medical Systems Biology (BIMSB), part of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC).

For the study, the research group cooperated with researchers from the Max Planck Institute for Infection Biology (MPIIB), Freie Universität Berlin, and Hong Kong University

SARS-CoV-2 uses a defense mechanism as a port of entry

Actually, the human body has a very effective defense mechanism against invaders, based on the interaction of various immune cells. T cells play an important role in this: When they encounter viruses in the organism, they destroy the affected cells.

They also secrete the signaling molecule interferon-gamma (IFN-γ). On the one hand, IFN-γ fights infectious agents. On the other hand, it calls other immune cells to the scene.

Heuberger and his colleagues have now shown how SARS-CoV-2 can turn this protective mechanism mediated by IFN-γ into its opposite. For in addition to immune cells, the body's mucous membrane cells also respond to IFN-γ by forming more ACE2 receptors.

SARS-CoV-2 needs these ACE2 receptors as a port of entry into the cells. Infected cells, in turn, make more ACE2. In this way, both the IFN-γ response of epithelial cells and the virus itself intensify the SARS-CoV-2 infection.

It took a year, science moves slowly

Drug trial that could improve respiratory recovery from COVID-19 now underway

https://medicalxpress.com/news…tory-recovery-covid-.html

A clinical trial has commenced this week to test whether a drug called Almitrine can help people who are seriously ill with COVID-19 to recover from the disease.

Patients suffering from COVID-19 pneumonia often develop very low levels of oxygen, called hypoxia, in the arterial blood supplying the body. Researchers from the University of Oxford hypothesize that the underlying problem is that the virus disrupts a normal process in the lungs called hypoxic pulmonary vasoconstriction, which diverts blood away from the diseased, non-functional parts of the lung and towards the parts of the lung that are still working properly. If the lungs are prevented from diverting blood to better-oxygenated lung segments, then this can cause the profound hypoxia from which patients with COVID-19 may die. The supportive therapy in hospitals aims to prevent this by using supplementary oxygen and ventilators to support breathing.

Almitrine bismesylate, a drug first developed in France, has been successful in treating acute respiratory distress syndrome by constricting the blood vessels in regions of the lung where the oxygen is low. Researchers say Almitrine could have the same effect in COVID-19 patients, with the potential to help restore the natural protective process in the lungs and increase oxygen levels in the arterial blood. The trial team hopes that administering this drug to COVID-19 patients will consequently reduce the amount of other respiratory support the patient needs.

According to the lead researcher Professor Peter Robbins, "The primary idea behind medical treatment is that it is supportive—its aim is to keep people alive while they make their recovery from the disease. In a way, you can view the potential support from Almitrine as extending people's individual runway to make a recovery from the disease. The idea behind our trial is to enhance the supportive treatment—extend people's runway."

The clinical trial commenced this week at the Royal Berkshire NHS Foundation Trust in Reading. Almitrine will be administered orally over a seven-day period to determine whether it is effective in reducing the need for other forms of ventilatory support.

Professor Robbins said, "I am pleased about our decision to use oral, rather than intravenous, almitrine for the trial. This lower tech approach could also be used in low- and middle-income countries which maybe have no, or insufficient, infrastructure to provide oxygen. As an oral drug, it really does have the potential to extend the runway to recovery for many people."

Clinicians aim to recruit in the region of 116 patients in total across three centers, starting with the first center, the Royal Berkshire Hospital, this week. The second and third centers will be the Oxford University Hospitals' John Radcliffe Hospital and University Hospital of Wales, Cardiff. The trial is expected to run for approximately 4 months.

Nicky Lloyd, Acting CEO of the Royal Berkshire NHS Foundation Trust, said, "This trial offers a great opportunity to supplement our increasing understanding of COVID-19 and meet the need for new, cost-effective treatments. The Royal Berkshire Hospital is a research-active hospital, which is well-placed to improve care and outcomes for our patients by taking part in collaborative research studies."

Dr. Nick Talbot, Chief Investigator for the overall trial across the three sites, added, "If Almitrine proves beneficial for our patients, we think it would represent a really important new approach in the management of COVID-19."

Coronavirus: is the Kent variant responsible for the rise in cases among young people in Israel and Italy?

https://news.google.com/articl…=en-US&gl=US&ceid=US%3Aen

At the start of the pandemic, one of the first questions scientists asked was: “What is the risk to children?” Information emerging from China was that – pre-existing conditions aside – the younger you are, the lower your risk of getting severe COVID. While children’s lives have been taken by the coronavirus, the numbers are low.

This mirrors the situation seen with influenza. Children do get sick with that virus, but the effects on pre-teens, if any, are much less severe than they are for adults. But that doesn’t mean that flu in children is not a problem – quite the contrary.

In the UK, children in primary school receive a flu vaccine that is sprayed up their noses. This is not done primarily to protect them from the relatively mild symptoms they may get – although that will happen – it is to reduce the chances of them getting infected and becoming mobile virus factories, infecting the adults around them. A child’s minor illness from flu could be lethal if transmitted to a grandparent.

In the early days of the pandemic, this low level of disease in children of all ages led to some assumptions that it was because they rarely caught the virus. When evidence started to appear that, in fact, they did catch the virus, the question of whether they could pass it on to adults was raised.

Knowing that children could be engines of virus spread caused some experts urged caution about declaring infection in pre-teens to not be a problem. While it was obvious from the numbers of people being admitted to hospital that childhood disease was far from the most pressing issue of the pandemic, the possibility that they might drive transmission was what caused schools to be closed.

LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2 In Vitro

https://www.biorxiv.org/content/10.1101/2020.12.02.408153v1

Abstract

Objective Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen accountable for the coronavirus disease 2019 (COVID-19) pandemic. Viral entry via binding of the receptor binding domain (RBD) located within the S1 subunit of the SARS-CoV-2 Spike (S) protein to its target receptor angiotensin converting enzyme (ACE) 2 is a key step in cell infection. The efficient transition of the virus is linked to a unique protein called open reading frame (ORF) 8. As SARS-CoV-2 infections can develop into life-threatening lower respiratory syndromes, effective therapy options are urgently needed. Several publications propose vitamin D treatment, although its mode of action against COVID-19 is not fully elucidated. It is speculated that vitamin D’s beneficial effects are mediated by up-regulating LL-37, a well-known antimicrobial peptide with antiviral effects.

Methods Recombinantly expressed SARS-CoV-2 S protein, the extended S1 subunit (S1e), the S2 subunit (S2), the receptor binding domain (RBD), and ORF8 were used for surface plasmon resonance (SPR) studies to investigate LL-37’s ability to bind to SARS-CoV-2 proteins and to localize its binding site within the S protein. Binding competition studies were conducted to confirm an inhibitory action of LL-37 on the attachment of SARS-CoV-2 S protein to its entry receptor ACE2.

Results We could show that LL-37 binds to SARS-CoV-2 S protein (LL-37/SStrep KD = 407 nM, LL-37/SHis KD = 414 nM) with the same affinity, as SARS-CoV-2 binds to hACE2 (hACE2/SStrep KD = 374 nM, hACE2/SHis KD = 368 nM). The binding is not restricted to the RBD of the S protein, but rather distributed along the entire length of the protein. Interaction between LL-37 and ORF8 was detected with a KD of 294 nM. Further, inhibition of the binding of SStrep (IC50 = 735 nM), S1e (IC50 = 168 nM), and RBD (IC50 = 126 nM) to hACE2 by LL-37 was demonstrated.

Conclusions We have revealed a biochemical link between vitamin D, LL-37, and COVID-19 severity. SPR analysis demonstrated that LL-37 binds to SARS-CoV-2 S protein and inhibits binding to its receptor hACE2, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 that protects from SARS-CoV-2 infection, and the therapeutic administration of vitamin D for the treatment of COVID-19 patients. Further, our results provide evidence that the direct use of LL-37 by inhalation and systemic application may reduce the severity of COVID-19.

Quote from JulianBianchi

Or that ivermectin would impact their multi-$100M sales of Mk-7110, MK-4482 and Rebif repurposed for COVID-19 treatment...

How could it impact on that if it does not work!?! That makes no sense. It would not cure anyone, so it would not reduce the demand for their other drugs.

If they thought it does work, surely they would be pleased to sell mountains of the stuff, at any price. A company does not turn down an opportunity to sell a product, even one that carnivalizes their own market. If they thought ivermectin works, they would know that if they do not sell it, someone else will. They can have part of the market, or none of it. Which would you choose?

Quote from JulianBianchi

Again, here is the science on ivermectin:

https://ivmmeta.com/

I'm still waiting for the first negative study of ivermectin on COVID-19, despite what you continue to claim....

Evidently the experts at Merck disagree with you. They say all of the studies are negative. I wouldn't know, but I expect they know more about this than you do.

Quote from zorud

Over 52 million doses of COVID-19 vaccines were administered in the United States from December 14, 2020, through February 14, 2021. During this time, VAERS received 934 reports of death* (0.0018%) among people who received a COVID-19 vaccine.

934 seems far too low. I guess they are not counting people who died from other known causes.

The vaccine is being administered mainly to old people, 65 and above. Such people often die. Let's assume 25 million people between the ages of 65 and 80 were vaccinated. Here is an actuarial table:

https://www.ssa.gov/oact/STATS/table4c6.html

This table shows that at age 65, 0.016 of the population will die within a year. That's 0.003 in 2 months. Distribute 25,000,000 people in the age cohorts from 65 to 80, and you find there are 1,857,123 in the 65-year-old bracket, and 1,177,020 in the 80-year-old bracket. 1,857,123 * 0.003 is 4,956 people. That's how many people at age 65 who will die in two months, out of a group of 25 million.