Snake Meat......source of chinese virus

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ACE (angiotensin-converting enzyme) blockade was mentioned in post #756 for maximakinin from the Chinese Red Belly toad, Bombina maxima. Ace blockade is also from the venom of Bothrops jararaca, which interesting history is here:

Snakes and Hypertension

https://www.anesthesiology.pubs.asahq.org/article.aspx?articleid=2588672

'....Bothrops jararaca....teprotide....saralasin.'

Linking another suspected COVID-19 intermediate host, is the venom from Bungarus flaviceps which does (not [italics]) interfere with ACE:

Isolation of the Major Lethal Toxin in the Venom of Bungarus flaviceps

Isolation of the major lethal toxin in the venom of Bungarus flaviceps - PubMed

The major lethal toxin in the venom of Bungarus flaviceps has been isolated by ion-exchange chromatography, absorption chromatography and RP-HPLC with a 14-fold purification and an overall yield of 16.5% of the lethal toxicity contained in crude venom. Its sublethal dose (LD(50)) determined in...

www.ncbi.nlm.nih.gov

'....The toxin has PLA activity but is free of ACE activity.'

If COVID-19's target receptor is ACE, it would likely choose Bungarus over Bothrops.

 

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Snakes and Hypertension

Snakes and Hypertension

Supplemental Digital Content is available in the text.

anesthesiology.pubs.asahq.org

 

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The vaccine is targeting the prefusion spike (before [italics]) conformational changes occur in either early or late endosomes mentioned earlier in the thread (as happens with Rab5 & Rab7 for Zika).

 

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Bombina-Hydroxychloroquine Trajectory

Jul 2020 COVID-19 Hydroxychloroquine Timeline of Evidence

Does hydroxychloroquine combat COVID-19? A timeline of evidence - PubMed

Does hydroxychloroquine combat COVID-19? A timeline of evidence

www.ncbi.nlm.nih.gov

'....Body Temperature Recovery Time, d*....(*= results are statistically significant)....Treatment Arm, 2.2, Control Arm, 3.2.'

Bombesin has controversial action. In some cases, it can lower body temperature by 5 degrees, in others, temp is increased.

Chinese Red Belly toad, Bombina maxima, was posted at #756 for maximakinin, ACE blockade for the Rab-ACE connection and bradykinin which is cleared by ACE.


Bombesin

Bombesin - Wikipedia

en.wikipedia.org

'....European Fire-Bellied Toad, Bombina bombina.'

In the study below, preoptic area resonates with conjunctivitis in COVID-19-suspected host, Cheremys.

Brs-3-Expressing Neurons / Body Temperature

Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake - PubMed

Bombesin-like receptor 3 (BRS3) is an orphan G-protein-coupled receptor that regulates energy homeostasis and heart rate. We report that acute activation of Brs3-expressing neurons in the dorsomedial hypothalamus (DMH^Brs3) increased body temperature (Tb), brown adipose tissue...

www.ncbi.nlm.nih.gov

'....We report that acute activation of (bombesin receptors) Brs-3-expressing neurons in the dorsomedial hypothalamus increases body temperature. We found that the preoptic area provides major input (excitatory and inhibitory) to DMH Brs-3 neurons.'

There is a link to cholecystokinin:

Cholecystokinin-Induced Desensitization

Cholecystokinin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas - PubMed

Incubating dispersed acini from guinea pig pancreas with cholecystokinin and then washing the cells to remove cholecystokinin reduced the subsequent stimulation of amylase secretion caused by pancreatic secretagogues, whose actions are mediated by release of cellular calcium (i.e...

www.ncbi.nlm.nih.gov

Bombesin-Induced Desensitization

Bombesin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas - PubMed

Incubating dispersed acini from guinea pig pancreas with bombesin and then washing the cells to remove bombesin reduced the subsequent stimulation of amylase secretion caused by bombesin, litorin, or ranatensin by as much as 80%, but did not alter the stimulation of amylase secretion caused by...

www.ncbi.nlm.nih.gov

 

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Bombesin Trajectory, continued

TRPV1 is a vanilloid receptor linked to pain.

Spinal Bombesin-Responsive Neurons/ Chloroquine / TRPV1

Role of spinal bombesin-responsive neurons in nonhistaminergic itch - PubMed

Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogen-evoked scratching behavior. We investigated whether spinal neurons that respond to intradermal (ID) injection of pruritogens also respond to spinal superfusion of bombesin and vice versa. Single-unit...

www.ncbi.nlm.nih.gov

'....chloroquine- and bombesin-sensitive spinal neurons signal itch from the skin.'

Superficial Dorsal Horn

Intradermal endothelin-1 excites bombesin-responsive superficial dorsal horn neurons in the mouse - PubMed

Endothelin-1 (ET-1) has been implicated in nonhistaminergic itch. Here we used electrophysiological methods to investigate whether mouse superficial dorsal horn neurons respond to intradermal (id) injection of ET-1 and whether ET-1-sensitive neurons additionally respond to other pruritic and...

www.ncbi.nlm.nih.gov

'....bombesin....chloroquine.'

Pubmed search 'trpv1 coronavirus' yields 2 references:

COVID-19 / TRPV1

The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis: A review - PubMed

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points...

www.ncbi.nlm.nih.gov

COPD / Smoking / TRPV1 Signaling

Flavonoids isolated from loquat (Eriobotrya japonica) leaves inhibit oxidative stress and inflammation induced by cigarette smoke in COPD mice: the role of TRPV1 signaling pathways - PubMed

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic...

www.ncbi.nlm.nih.gov

 

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Further underscoring the importance of Dr. Zelenko's addition of zinc, is this study:

Jun 2020 Zinc Additives May Be Required

Improving the efficacy of Chloroquine and Hydroxychloroquine against SARS-CoV-2 may require Zinc additives - A better synergy for future COVID-19 clinical trials - PubMed

The recent outbreak of coronavirus disease 2019 (COVID-19), is now officially declared as a pandemic by the World Health Organization. As of now, there is no known effective pharmaceutical agent against the SARS-CoV-2 virus. However, several precautionary measures have been prescribed to prevent...

www.ncbi.nlm.nih.gov

 

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Posted in #765 was the resiniferatoxin link to COVID-19:

COVID-19 / TRPV1 / Resiniferatoxin

https://www.ncbi.nlm.nih.gov/32292906

on that Pubmed page are similar articles, and the reader can see the kinnin link to bombesin and bradykinin:

Kallikrein-Kinin Blockade

Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome - PubMed

COVID-19 patients can present with pulmonary edema early in disease. We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed...

www.ncbi.nlm.nih.gov

Resiniferatoxin

Resiniferatoxin - Wikipedia

en.wikipedia.org

Euphorbia resinifera

Euphorbia resinifera - Wikipedia

en.wikipedia.org

The 'original' Pubmed entry for resiniferatoxin, (although we have yet to confirm the chronological order), is here:

Casein kinase II regulates N-methyl-D-aspartate receptor activity in spinal cords and pain hypersensitivity induced by nerve injury - PubMed

Increased N-methyl-d-aspartate receptor (NMDAR) activity and phosphorylation in the spinal cord are critically involved in the synaptic plasticity and central sensitization associated with neuropathic pain. However, the mechanisms underlying increased NMDAR activity in neuropathic pain...

www.ncbi.nlm.nih.gov

'....mediated by GABA and glycine in the spinal cord through increased proteolysis of K+-Cl-cotransporter-2 mediated by calpain.'

GABA and glycine link aspartate, above. In post #702 of 9 Jul 2020, was shown the COVID mutation and the dengue link, though the latter could be a coincidence. COVID-19 mutation was from aspartic acid 614 to glycine 614.

Snake Meat......source of chinese virus

This today from Avian Flu Talk: Kazakhstan: Unknown Pneumonia Deadlier Than COVID-19 https://www.scmp.com/news/china/diplomacy/article/3092563/chinese-embassy-warns-deadly-unknown-pneumonia-kazakhstan '....death rate of this disease is much higher than the novel coronavirus.'

www.usmessageboard.com

We are yet to verify the abstract #, though here is an intriguing link to Chrysemys conjunctivitis and its ACE2 receptors:

'remdesivir, aerosol antiviral in humid heat vaporization....together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8-5% conjunctival congestion) would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV & V, reducing hospitalization and therefore death.'

 

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COVID-19 / TRPV1

The role of afferent pulmonary innervation in ARDS associated with COVID-19 and potential use of resiniferatoxin to improve prognosis: A review - PubMed

Acute respiratory distress syndrome (ARDS) is one of the major causes of mortality associated with COVID-19 disease. Many patients will require intensive care with ventilatory support. Despite progress and best efforts, the mortality rates projected remain high. Historical data outlook points...

www.ncbi.nlm.nih.gov

 

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The remdesivir excerpt of post #767 (Boston/Italy, dated Nov 2020) is here:

A new pharmacological approach based on remdesivir aerosolized administration on SARS-CoV-2 pulmonary inflammation: A possible and rational therapeutic application - PubMed

The new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over...

www.ncbi.nlm.nih.gov

 

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We've already mentioned the Lombardian chikungunya outbreak of 2007.

Anti-Chikungunya Resiniferatoxin

LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity - PubMed

Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11...

www.ncbi.nlm.nih.gov

Jun 2019 Macrocyclic Diterpenoids / Chikungunya

Macrocyclic Diterpenoids from Euphorbiaceae as A Source of Potent and Selective Inhibitors of Chikungunya Virus Replication - PubMed

Macrocyclic diterpenoids produced by plants of the Euphorbiaceae family are of considerable interest due to their high structural diversity; and their therapeutically relevant biological properties. Over the last decade many studies have reported the ability of macrocyclic diterpenoids to...

www.ncbi.nlm.nih.gov

Since the thyroid is the sexual gland par excellence, and since there is also an iodinated resiniferatoxin, we re-mention the Chrysemys thyroid link:

Chrysemys / Thyroid / Chloroquine

Specific uptake, dissociation, and degradation of 125I-labeled insulin in isolated turtle (Chrysemys dorbigni) thyroid glands - PubMed

Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with 125I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of...

www.ncbi.nlm.nih.gov

Hydroxychloroquine is anti-chikungunya, though chloroquine enhances chikungunya:

May 2018 Chloroquine-Enhanced Chikungunya

Paradoxical Effect of Chloroquine Treatment in Enhancing Chikungunya Virus Infection - PubMed

Since 2005, Chikungunya virus (CHIKV) re-emerged and caused numerous outbreaks in the world, and finally, was introduced into the Americas in 2013. The lack of CHIKV-specific therapies has led to the use of non-specific drugs. Chloroquine, which is commonly used to treat febrile illnesses in the...

www.ncbi.nlm.nih.gov

 

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It is finally pleasing to connect the hepatitis excerpts so far in this thread, with the discoverer of the Australian antigen and head of NASA Astrobiology, Baruch S. Blumberg. This is also a Wuhan connection, and note the dates:

8 Jul 2020 Beijing, Baruch S. Blumberg Hepatitis B Foundation, Western University, London, Ontario, GILT / SARS-Cov-2

LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2 - PubMed

C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an...

www.ncbi.nlm.nih.gov

'gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT)....'

This is also a connection to the second suspected intermediate COVID-19 host, Pelodiscus sinensis, recalling that this turtle soup was being fed to quarantined Wuhanians (previous post).

Jan 2019 Pelodiscus / GILT (Wuhan State Key Laboratory of Freshwater Ecology, Jiangxi Normal University)

Identification and characterization of the interferon-γ-inducible lysosomal thiol reductase gene in Chinese soft-shelled turtle, Pelodiscus sinensis - PubMed

The reduction of disulfide bonds of exogenous antigens is crucial to the MHC-II class antigen processing and presenting pathway and is catalysed by interferon-γ-inducible lysosomal thiol reductase (GILT). In this study, a reptile GILT gene from Chinese soft-shelled turtle, Pelodiscus sinensis...

www.ncbi.nlm.nih.gov

 

[badger2]

From the LY6E trajectory one finds CD59:

1990 CD59

The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility - PubMed

A cDNA encoding the human leukocyte antigen CD59 has been isolated from the erythroid cell line K-562 and its identity confirmed through expression in COS cells. Northern blotting reveals three message species of approximately 800, 1400 and 2000 bases in size, which are constitutively expressed...

www.ncbi.nlm.nih.gov

Nov 2019 CD59 / SNARE / Insulin Exocytosis

A cryptic non-GPI-anchored cytosolic isoform of CD59 controls insulin exocytosis in pancreatic β-cells by interaction with SNARE proteins - PubMed

CD59 is a glycosylphosphatidylinositol (GPI)-anchored cell surface inhibitor of the complement membrane attack complex (MAC). We showed previously that CD59 is highly expressed in pancreatic islets but is down-regulated in rodent models of diabetes. CD59 knockdown but not enzymatic removal of...

www.ncbi.nlm.nih.gov

The SNARE trajectory leads back to Rab7 and Charcot-Marie-Tooth, previous post, on the following page of the same chapter via Epstein's Inborn Errors of Development:

'The first disease-causing mutations in SNARE proteins were recently discovered. A deletion in the gene encoding SNAP-29 was found to cause neurocutaneous CEDNIK syndrome (Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome).....FHL, the second SNARE defect identified, is cause by mutations in syntaxin 11 or Munc13-4. Munc13-4 is a Rab27a effector involved in mast cell degranulation.

Rab27a acts as a component of the myosin 5a receptor on melanosomes, and the Rab27a-myosin 5a int5eraction is mediated by melanophilin. Rab27a is also expressed in cytotoxic T-lymphocytes....'
(Epstein, op cit)

Recalling that the Chrysemys thyroid and chloroquine study (previous post) linked insulin:

Specific uptake, dissociation, and degradation of 125I-labeled insulin in isolated turtle (Chrysemys dorbigni) thyroid glands - PubMed

Thyroid glands from turtles (Chrysemys dorbigni) pretreated with potassium iodide were incubated with 125I-insulin in the presence or absence of unlabeled insulin, in order to study its specific uptake. At 24 degrees, the specific uptake reached a plateau at 180 min of incubation. The dose of...

www.ncbi.nlm.nih.gov

 

[badger2]

From Promedmail, we learn more on COVID-19 mutations:

Enhanced Transmission

https://www.medrxiv.org/content/10.1101/2020.07.13.20152959v1.full.pdf

'....In Western Europe, the A23403G-C14408T subclade dominated while in the U.S., the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California....We postulated that in areas with high numbers of these co-circulating subclades, a person may be serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity who may mount insufficient levels of neutralizing antibodies against the first infection. Further studies are necessary, but the implications of such a mechanism will need to be considered for all current COVID-19 vaccine designs.

C14408T = RNA-dependent RNA polymerase

A23403G = spike protein gene

G25563T = Orf1a

 

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The report above continues:

'The third subclade contained an additional missense nucleotide substitution in Orf3a (G25563T). These missense mutations led to non-conservative amino acid substitutions in the spike protein (D614G), RNA-dependent RNA polymerase (P323L), and Orf3a protein (Q57H).
....
In U.S., most of the sequence submissions were from New York and California. The proportion of A23403G-C14408T mutant in San Diego vs San Francisco was 18.9% vs 14.3%, respectively, while the frequencies of the A23403G-C14408T-G25563T were 66.7% vs 41.6%, respectively.

To determine where the subclades originated, we examined the sequences deposited from China. Of 742 sequences from China deposited mostly from Jan through Mar, we found 15 (2%) A23403G, 19 (2.6%) A23403G-C14408T and 8 (1.1%) A23403GC14408T-G25563T strains. Thus the latter two dominant nucleotide variants in Europe and the U.S. most likely originated in China and greatly expanded in these regions.

Interestingly, in California that had a relatively low CFR, the epidemic started with the triple mutant clade, but by May, the A23403G-C14408T mutant took over.'

 

[badger2]

More good COVID-19 news.
1 hr. ago
Oxford's Vaccine

Oxford’s COVID-19 vaccine is starting to look like a winner

Oxford researchers have developed a potential vaccine for COVID-19. Early testing in more than 1,000 clinical trial participants indicates the treatment is both safe and effective. Epidemiology breakthroughs aren’t our usual subject matter here at TNW, but the opportunity to finally publish...

www.aol.com

 

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The Lancet Report of post #775:

'In the ChAdOx1 nCoV-19 groups, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single does when measured in MNA 80 and in 35 (100%) participants when measured in PRNT 50. After a booster does, all participants had neutralising activity (nine of nine in MNA 80 at day 42 and ten of ten in Marburg VN on day 56).'

 

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Remarkably, a Pubmed search, 'spike-specific t-cells,' retrieves only one reference, and that reference has 60 co-authors! We mentioned the RBD in posts #174 and #633.

Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients - PubMed

COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from...

www.ncbi.nlm.nih.gov

 

[badger2]

We mentioned the music in post #759, and it's available as well for the study of ebola vaccine:

9 Jun 2020 CTL Peptide Vaccine / COVID-19

An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design - PubMed

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV...

www.ncbi.nlm.nih.gov

'....We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse-adapted EBOV challenge.'

 

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The ebola vaccine, above, is co-authored by

1. Flow Pharma (California)
2. La Jolla Institute of Allergy and Immunity (California)
3.Columbia University, New York
4. University of Texas
5. Sao Paulo, Brazil
6. University of Macau (China)
7.Massachusetts General Hospital
A COVID-19 link to these institutions would be Brain Foley (Los Alamos National Labs) who was at one time, if not mistaken, at La Jolla.

 

[Desperado]

So now it is snake meat!!!! What happen to the theory of Wuhan Bat Wings? keep making up phony stories and give China a pass on a biological attack on the US