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

[badger2]

The evidence suggests that COVID-19-vaccinated Chinese miners proposed for New Guinea kuru country was more than a coincidence, and here we link the all-important lysosome in chloroquine-hydroxychloroquine pharmacodynamics to prion disease:

Lysosomal Quality Control / Prions

Lysosomal Quality Control in Prion Diseases - PubMed

Prion diseases are transmissible, familial or sporadic. The prion protein (PrP), a normal cell surface glycoprotein, is ubiquitously expressed throughout the body. While loss of function of PrP does not elicit apparent phenotypes, generation of misfolded forms of the protein or its aberrant...

www.ncbi.nlm.nih.gov

'....the lysosomal quality control machinery emerges as one of the primary targets exploited by the disease-causing isoforms.'

 

[badger2]

In long-term experimental chloroquine myopathy, prion proteins accumulate:

Kyushu / Experimental Chloroquine Myopathy

Accumulation of prion protein in muscle fibers of experimental chloroquine myopathy: in vivo model for deposition of prion protein in non-neuronal tissues - PubMed

Prion protein (PrP) is known to accumulate in some non-neuronal tissues under conditions unrelated to prion diseases. The biochemical and biological nature of such accumulated PrP molecules, however, has not been fully evaluated. In this study, we established experimental myopathy in hamsters by...

www.ncbi.nlm.nih.gov

'....PrP accumulation was immunohistochemically demonstrated in autophagic vacuoles in degenerated muscle fibers.'

 

[badger2]

Nervous necrosis virus was mentioned in post #979. Pubmed search, 'nervous necrosis virus bream,' because white bream virus is related to coronaviruses, mentioned in The Nidoviruses: Coronaviruses and Arteriviruses. The search yields entries for Gilthead Sea Bream, Sparus aurata. This will link to polyoma viruses in Canadian bats as well as Myotis californicus. Note the asymptomatic aspect of this infection:

White Bream Nidovirus

Genetic analysis of a novel nidovirus from fathead minnows - PubMed

A bacilliform virus was isolated from diseased fathead minnows (Pimephales promelas). Analysis of the complete genome coding for the polyprotein (pp1ab), spike (S), membrane (M) and nucleocapsid (N) proteins revealed that the virus was most like white bream virus (WBV), another bacilliform virus...

www.ncbi.nlm.nih.gov

Nervous Necrosis Virus / Sparus aurata

Prevalence of nervous necrosis virus (NNV) and Streptococcus species in wild marine fish and crustaceans from the Levantine Basin, Mediterranean Sea - PubMed

Infectious diseases in marine animals have ecological, socio-economic and environmental impacts. Nervous necrosis virus (NNV) and Streptococcus iniae have become major threats to marine aquaculture and have been detected in morbid marine organisms worldwide. However, despite their importance...

www.ncbi.nlm.nih.gov

Sparus aurata / Nodavirus / Asymptomatic

Sea bream Sparus aurata, an asymptomatic contagious fish host for nodavirus - PubMed

During an epidemiological survey of viral encephalopathy and retinopathy (VER) in diseased sea bass Dicentrarchus labrax, a nodavirus isolate was recovered from net pen-reared sea bream Sparus aurata harboured in the same farming premises. After the virus was isolated and identified by...

www.ncbi.nlm.nih.gov

SaPYV1

Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream - PubMed

Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the...

www.ncbi.nlm.nih.gov

Polyoma Coronavirus / Canadian Bats / Myotis californicus

Detection of polyoma and corona viruses in bats of Canada - PubMed

Several instances of emerging diseases in humans appear to be caused by the spillover of viruses endemic to bats, either directly or through other animal intermediaries. The objective of this study was to detect, identify and characterize viruses in bats in the province of Manitoba and other...

www.ncbi.nlm.nih.gov

We mentioned interferon-stimulated gene 15 in posts # 630 and # 733:

Sparus aurata Interferon-Stimulated Gene

Identification of an interferon-stimulated gene, isg15, involved in host immune defense against viral infections in gilthead seabream (Sparus aurata L.) - PubMed

Interferons (IFNs) play a key role in the innate immunity of vertebrates against viral infections by inducing hundreds of IFN-stimulated genes (ISGs), such as isg15. Isg15 is an ubiquitin-like protein, which can conjugate cellular and viral proteins in a process called ISGylation, although it...

www.ncbi.nlm.nih.gov

 

[badger2]

The link in post #631 is incorrectly transcribed, though is the link to ebola vaccine (vesicular stomatitis virus) as well as heron hepatitis virus:

Nodamura Virus

Enhanced susceptibility of cancer cells to oncolytic rhabdo-virotherapy by expression of Nodamura virus protein B2 as a suppressor of RNA interference - PubMed

Antiviral responses are barriers that must be overcome for efficacy of oncolytic virotherapy. In mammalian cells, antiviral responses involve the interferon pathway, a protein-signaling cascade that alerts the immune system and limits virus propagation. Tumour-specific defects in interferon...

www.ncbi.nlm.nih.gov

 

[badger2]

We learn from post #630 that nsp3 (non-structural protein 3) is the largest in the coronavirus genome. We searched, 'nsp3 covid-19' and retrieved an eye-catching report from Brazilian dermatology:

Jul 2020 Brazil COVID-19 / Dermatology

Lessons from dermatology about inflammatory responses in Covid-19 - PubMed

The SARS-Cov-2 is a single-stranded RNA virus composed of 16 non-structural proteins (NSP 1-16) with specific roles in the replication of coronaviruses. NSP3 has the property to block host innate immune response and to promote cytokine expression. NSP5 can inhibit interferon (IFN) signalling and...

www.ncbi.nlm.nih.gov

'....polymorphous cutaneous lesions....blue toe....'

COVID-19 and blue toes was mentioned in the USMB thread titled, "Blue Toes or Blue Fingertips Could Mean You Have the Virus!" Thus murine hepatitis coronavirus links ISG-15, NF-kappaB and blue toe in COVID-19.

 

[badger2]

In this Icelandic report, antibodies against C-19 are produced in waves:

2 Sept 2020 Iceland COVID-19 Study

Large COVID-19 study from Iceland has good news on enduring antibody protection, vaccine prospects

A study of more than 30,000 people in Iceland found that antibodies produced after a COVID-19 infection last for at least four months, researchers reported Tuesday in the New England Journal of Medicine. Previous studies have suggested antibody protection wears off quickly, but most of those...

news.yahoo.com

'....a second wave of antibodies forms and grows steadily during the first two months after infection.'

 

[badger2]

The Oxford vaccine results will take a while:

Large trials for anticipated Oxford COVID-19 vaccine begin in the U.S.

Despite pressure from the White House, researchers may not be able to say whether the vaccine works until after the election.

news.yahoo.com

'....University of Wisconsin is one of dozens of test sites in U.S....doesn't expect preliminary data until at least Thanksgiving.'

 

[BigDave]

Snake meat sounds like an interesting dinner idea

 

[badger2]

Bret Weinstein's video, "Why COVID-19 May Have Leaked From A Lab," mentions furin site and two arginines, the arginines apparently not occurring in nature, at timepoint 5:40. This is the argument for a lab-designed virus, though Weinstein's credibility becomes questionable when we find a coronavirus expert, Foley, linked to La Jolla, California, also the location of a double-arginine report:

Bret Weinstein: Why COVID-19 May Have Leaked From A Lab

'....one of the enhancements....furin site....arginine....'

(1994) Scripps Research Institute, La Jolla, California / RR Motif Arginines

An N-terminal double-arginine motif maintains type II membrane proteins in the endoplasmic reticulum - PubMed

Use of alternative initiator methionines in human invariant (Ii) chain mRNA results in the synthesis of two polypeptides, Iip33 and Iip31. After synthesis both isoforms are inserted into the endoplasmic reticulum (ER) as type II membrane proteins. Subsequently, Iip31 is transported out of the...

www.ncbi.nlm.nih.gov

'....RR-tagged transferrin receptor partially localized to the intermediate compartment....'

 

[badger2]

The transferrin link adds some genes to the list:

Jul 2020 Is Transferrin A Missing Link?

COVID-19-Related Coagulopathy-Is Transferrin a Missing Link? - PubMed

SARS-CoV-2 is the causative agent of COVID-19. Severe COVID-19 disease has been associated with disseminated intravascular coagulation and thrombosis, but the mechanisms underlying COVID-19-related coagulopathy remain unknown. The risk of severe COVID-19 disease is higher in males than in...

www.ncbi.nlm.nih.gov

 

[badger2]

Here we link Robin Williams and lewy body dementia to chloroquine. Because potential intermediate COVID-19 hosts and models include the porpoise and hamster, respectively (previous posts) and this intermediate C-19 host list includes Bovidae, a video of interest is Robin Williams, "Dolphin Evolution."

youtube.com/watch?v=Bqj2JnwodqM

4 Sept 2020 Tom Seaver-Robin Williams Lewy Body Dementia

Tom Seaver, like Robin Williams, had Lewy body dementia, but what is this strange illness? A neurologist explains

Lewy body dementia was highlighted in the news twice this week with the death of Hall of Fame pitcher Tom Seaver from Lewy body dementia complications and the release of “Robin’s Wish,” a documentary about Robin Williams’ final years, when the actor lived with Lewy body dementia. Seaver died...

news.yahoo.com

Greece, Hungary, Germany, California / Chloroquine / Lewy Bodies

Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype - PubMed

The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the...

www.ncbi.nlm.nih.gov

'....The autophagy-lysosome pathway (ALP) regulates the intracellular homeostasis of the cytosolic protein SNCA/alpha synuclein, which is tightly linked to age-related neurodegenerative synucleinopathies, including Parkinson;s disease (PD) and dementia with lewy bodies (DLB)....endosomal sorting complex required for transport (ESCRT) complex....Treatment with 50 microM of the ALP inhibitor chloroquine (CQ) also upregulated total extracellular SNCA (synuclein alpha) levels by 2.5-fold....We found that 20 nM Baf (bafilomycin) led to approximately 20% fewer cells while no cell loss was observed with CQ. In each of the conditions assessed, more than 95% of cells detected were trypan blue negative, and therefore intact....In contrast, the ALP inducer, rapamycin, had no influence on extracellular SNCA levels....several ALP-related components were identified in extracellular vesicles....LAMP2....in H4 EVs: Rab11.'

 

[badger2]

One of these URLs should function in the spacebar:





With the furin cleavage site of previous posts, there will be ebola, Zika, and fruit-bat parainfluenza connections. With the Rab11 of post #991, there will be a Zika connection to Rab5 in the Warburg Micro and Martsolf Syndromes, which mostly concerns Rab3GAP1 and RAB3GAP2. In these latter syndromes, of interest are the GTP-linked geranylgeranyl moieties, which have a relation to SARS-CoV-2, in this study:

SARS-CoV-2

Boning up: amino-bisphophonates as immunostimulants and endosomal disruptors of dendritic cell in SARS-CoV-2 infection - PubMed

Amino-bisphosphonates such as zoledronic acid (ZA) can possibly ameliorate or prevent severe COVID-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ T cell expansion, important in the acute response in the lung; (2) as DC modulators, limiting their...

www.ncbi.nlm.nih.gov

 

[badger2]

We make the geranylgeranyl connection in coronaviruses because one symptom in Micro syndrome is, like Zika infection, microcephaly.

Boning up: amino-bisphophonates as immunostimulants and endosomal disruptors of dendritic cell in SARS-CoV-2 infection - PubMed

Amino-bisphosphonates such as zoledronic acid (ZA) can possibly ameliorate or prevent severe COVID-19 disease by at least three distinct mechanisms: (1) as immunostimulants which could boost γδ T cell expansion, important in the acute response in the lung; (2) as DC modulators, limiting their...

www.ncbi.nlm.nih.gov

'....ZA (zoledronic acid) could plausibly attack the endosomal trafficking central to SARS-CoV-2 infection. ZA inhibits the prenylation of small guanine-nucleotide-binding regulatory proteins (G-proteins) such as Rab family members through inhibition of geranylgeranyl transferases. Rab GTPase family members are involved in endosomal trafficking, including compartmentalization into early, recycling, late and lysosomal routes.'

 

[badger2]

Further on the transferrin trajectory, there is....

Is Transferrin A Missing Link?

'....ADAMTS13, F11, HGFAC, KLKB1 (procoagulants), two anticoagulants C1QTNF1, SERPINA5....expression of procoagulant transferrin (not associated with the Gene Ontology term, "blood coagulation") was higher in males, increased with age, and was upregulated upon SARS-CoV-2 infection.

The Italians were looking for scrapie in porpoise brains, though there are no published reports of this having occurred.

Transferrin / Prion / Scrapie

Change in the characteristics of ferritin induces iron imbalance in prion disease affected brains - PubMed

Prion disease associated neurotoxicity is mainly attributed to PrP-scrapie (PrP(Sc)), the disease associated isoform of a normal protein, the prion protein (PrP(C)). Participation of other proteins and processes is suspected, but their identity and contribution to the pathogenic process is...

www.ncbi.nlm.nih.gov

....Emerging evidence implicates an imbalance of brain iron homeostasis as a significant cause of prion disease-associated neurotoxicity....The underlying cause is change in the characteristics of ferritin, an iron-storage protein that becomes aggregated, detergent insoluble, and partitions with denatured ferritin using conventional methods of ferritin purification. A similar phenotype of iron deficiency is noted in lumbar spinal cord (SC) tissue of scrapie-infected hamsters, a site unlikely to be affected by massive neuronal death and non-specific iron deposition. As a result, the iron uptake protein, transferrin (tf) is upregulated in scrapie-infected SC tissue, and increases with disease progression.'

 

[badger2]

In post #991 was posted the chloroquine/lewy body study. To make the snake connection, we first excerpt from that study:

Autophagy inhibition promotes SNCA/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype - PubMed

The autophagy-lysosome pathway (ALP) regulates intracellular homeostasis of the cytosolic protein SNCA/alpha-synuclein and is impaired in synucleinopathies, including Parkinson disease and dementia with Lewy bodies (DLB). Emerging evidence suggests that ALP influences SNCA release, but the...

www.ncbi.nlm.nih.gov

....Several ALP-related protein components were identified in extracellular vesicles: LAMP2 (lysosomal associated membrane protein 2) and HSPA/HSP70 (heat-shock protein 70) could specifically be correlated with Alzheimer's disease progression....in H4 extracellular vesicles: Rab11....sumoylation, previously shown to stimulate the ALP-mediated degradation of SNCA, directs its sorting to vesicles....using PC 12 cells, the process of exophagy was proposed to underlie increase of extracellular SNCA in conditional media fractions positive for the late endosome/amphisome markers ANXA5 and Rab27a.'

"Late" Macroendosomes and Acidic Endosomes in Vertebrate Motor Nerve Terminals

"Late" macroendosomes and acidic endosomes in vertebrate motor nerve terminals - PubMed

Activity at the vertebrate nerve-muscle synapse creates large macroendosomes (MEs) via bulk membrane infolding. Visualized with the endocytic probe FM1-43, most (94%) of the ∼25 MEs/terminal created by brief (30-Hz, 18-second) stimulation dissipate rapidly (∼1 minute) into vesicles. Others...

www.ncbi.nlm.nih.gov

'....Garter snake, Thamnophis sirtalis, were housed as previously described....were rapidly sacrificed by decapitation....AEs (acidic endosomes) share biochemical and immunohistochemical markers (e.g., lysosome-associated membrane protein 1 [LAMP-1])....Based on our data, we propose that MEs (macroendosomes) serve as sorting endosomes.'

 

[badger2]

Rattlesnakes (post #988) also link to lysosomes:

Cytotoxic effects of crotamine are mediated through lysosomal membrane permeabilization - PubMed

Crotamine, one of the main toxic components of Crotalus durissus terrificus venom, is a small non-enzymatic basic polypeptide, which causes hind limb paralysis and necrosis of muscle cells. It is well-known that several toxins penetrate into the cytosol through endocytosis, although in many...

www.ncbi.nlm.nih.gov

'....Overall, our data suggests that lysosomes are the primary targets for crotamine toxicity.'

Crotoxin / MCF-7 Breast Cancer
htps://www.ncbi.nlm.nih.gov/pubmed/17376294

 

[badger2]

This is the URL showing at Pubmed:

pubmed.ncbi.nlm.nih.gov/pubmed/17376294/

 

[badger2]

Adding a 't' to the URL:

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells - PubMed

An autophagic mechanism contributes to the apoptosis of MCF-7 cells induced by CrTX.

www.ncbi.nlm.nih.gov

 

[badger2]

In the chloroquine-lewy body study linking LAMP2, Table 1. Clicking on that link will include another asymptomatic entry as well as another arginine entry for the COVID-19 files:

DAND Arg-321 / Asymptomatic HyperCKemia / TLR7/9

Asymptomatic hyperCKemia in a case of Danon disease due to a missense mutation in Lamp-2 gene - PubMed

Primary lysosome-associated membrane protein-2 (LAMP-2) deficiency is an X-linked disease, characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and mental retardation, previously known as Danon disease. Mutations of lamp-2 gene have been reported so far in about 20 patients...

www.ncbi.nlm.nih.gov

Using a TLR7 search, there is thus a connection to the COVID-19 hyperimmune response:

COVID-19 / TLR7

https://www.ncni.nlm.nih.gov/pubmed/32361001

'....An immunoinformatic approach showed that the SARS-CoV-2 genome has more ssRNA fragments that could be recognized by TLR7/8 than the SARS-CoV genome. These findings suggest innate immune hyperactivation by SARS-CoV-2....possibly able to provoke a robust inflammatory response via TLR7/8 and cause acute lung injury.'

 

[badger2]

Bioinformatic analysis and identification of single-stranded RNA sequences recognized by TLR7/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV genomes - PubMed

During virus infection, host toll-like receptors (TLRs) can recognize different pathogen-associated molecular patterns and trigger the innate immune response. TLR7/8 can identify the single-stranded RNA (ssRNA) of the virus. This study aimed to search ssRNA sequences recognized by TLR7/8 from...

www.ncbi.nlm.nih.gov