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

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In post #478 we noted dephosphorylation and phosphorylation sites linked to Homo sapiens HDAC1 and chloroquine, which full text we cannot access. In the Bologna COVID-19 study (post #313), the serine-to-leucine at position 84 of COVID-19 ORF8:

'We analyzed the alternative isoforms of COVID-19 ORF8-aa84, dubbed ORF8-L (Leucine) and ORF8-S (Serine). Unfortunately, no crystal structures of close homologs to the ORF8 protein are available for a reliable homology modelling to measure the structural impact of this aminoacidic substitution. The closest 3D model to COVID-19 ORF8 available in Protein Data Bank is a short 22 amino acid stretch in the protein entry 6P65, with a non-significant E-value of 0.848. We therefore employed de novo methods to infer structural features of ORF8. One important effect we we could detect is a significant effect of Serine in ORF8-S in inducing structural disorder in the protein C-terminal portion, which is not predicted to be present in the ORF8-L, using the Russell/Linding algorithm. Moreover, it did not escape our attention that the ORF8-S could theoretically generate a novel phosphorylation target for the mammalian host Serine/Threonine kinases of the host organism. So, we searched for ORF8 homologous substrates in the Mammalia NCBI nr protein database, but could not find matches within E-value threshold of 1.'
(Ceraolo/Giorgi, Genomic Variance of the 2019-nCoV Coronavirus, op cit)

 

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We pick up the Shanghai/Autophagy/Chloroquine link to FOXO3A (post #478) with this FOXO excerpt:

'Like DAF-16 in Caenorhabditis elegans, which is involved in longevity, the FOXO subfamily( Foxo1, Foxo3, Foxo4) are involved in the regulating of the cell cycle and apoptosis. The unique feature of this subfamily is the cytoplasmic nuclear relocalization of the Fox protein. The most convincingly demonstrated substrates for PKB.Akt are the FOXO subfamily of forkhead transcription factors. The phosphorylation of FOXO proteins results in their binding to 14-3-3 proteins and then their expulsion from the nucleus causing a loss of transcriptional activity and a decreased expression of proteins promoting cell death and cell cycle arrest. It has recently been shown that mammalian FOXO proteins function in cell cycle arrest, cell death, DNA repair, metabolism and protection from oxidative stress. Overall, FOXO proteins regulate the resistance of cells to stress and they may also affect the organism lifespan.'
(Miura N, et al, The Forkhead Gene Family, in Inborn Errors of Development, op cit)

Before linking chloroquine to angiotensin, we next link chloroquine to FOXP3 and FOXP3 to ACE2:

National Center for Biotechnology Information

Ohio State University, Wooster / ACE2 / FOXP3 / Tryptophan
Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gn... - PubMed - NCBI
'....supplementation increased the frequencies of regulatory (CD+4, or CD+8 CD25+ FOXP3+) T cells in pigs on both sufficient and deficient diets.'

Recalling that Chinese doctors were saying that COVID-19 reinfection was deadly, due to cardiac injury via treatment with certain drugs....

Chloroquine / Angiotensin / SQSTM1 Major Regulator of Autophagy (Cost: $51/24 Hours; $312/30 Days)
(Florida State University, Tallahassee; Emory, Atlanta; U. of California, Irvine, Case Western, and Harrington Heart and Vascular Institute, Cleveland)
SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. - PubMed - NCBI

Feb 2019 Santiago-Dallas / ACE2-Regulated Autophagy
Angiotensin II-Regulated Autophagy Is Required for Vascular Smooth Muscle Cell Hypertrophy. - PubMed - NCBI
'....These findings were confirmed by the assessment of autophagic flux by co-administering Ang II together with chloroquine (30 mM).'

Dec 2018 Fourth Military Medical University, Xian, China / Angiotensin II-Induced Cardiac Injury
Mst1 knockout enhances cardiomyocyte autophagic flux to alleviate angiotensin II-induced cardiac injury independent of angiotensin II receptors. - PubMed - NCBI
'....in the presence and absence of chloroquine....'

Nov 2017 Jinan, China / Role of Psychological Stress on Heart Autophagy
The Role of Psychological Stress on Heart Autophagy in Mice With Heart Failure. - PubMed - NCBI
'....chloroquine and rapamycin were used to detect autophagic flux....'

 

[badger2]

Vascular senescence (#482) links organism lifespan (# 482), and COVID-19 recognizes ACE2 receptors (#482).

 

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Current stats, 2,459 deaths (post #279)

 

[badger2]

One of these should work:

AFT: Update Italy
(URL as found)
reuters.com/article/china-health-italy/update-2-italys-coronavirus-outbreak-infects-51-people-kills-2-idUSL5N2AM076

(first alternate URL)
UPDATE 4-Two dead, 79 infected in Italy as govt fights to contains coronavirus outbreak

(second alternate URL)
UPDATE 4-Two dead, 79 infected in Italy as govt fights to contains coronavirus outbreak

 

[badger2]

Avian Flu Talk: 3 hrs, 55 min. ago: 'We're now going to Defcon 6 and declaring a pandemic. The WHO will declare it shortly, but not waiting for it."

 

[badger2]

This was about 10 hours ago:

22 Feb 2020 CDC is Preparing for the 'Likely' Spread of Coronavirus in the U.S.
(URL as found)
news.yahoo.com/theres-still-fighting-chance-contain-170857481.html

CDC is preparing for the 'likely' spread of coronavirus in the US, officials say

CDC is preparing for the 'likely' spread of coronavirus in the US, officials say

 

[badger2]

The two deaths on the ship were Japanese, meaning that COVID-19 had many ACE2 receptors to choose from in each of the two hosts (previous Japanese stats for highest number of ACE2 receptors in lung:

 

[badger2]

@ timepoint 3:11

 

[badger2]

Avian Flu Talk

'Today, early on the 23rd of Feb, there are 2,023 international confirmed cases outside of China, as projected (to the day [italics]) way back on 8 Feb, by the exponential model. Other models, as we have refined them, have been close as well....Watch for a shift in initial messaging from your local authorities from "containment" to "mitigation." That's your signal the authorities have concluded it will be everywhere near you soon....You're welcome Kim and others. I saw this thread had 16,000 views....What is definitely going to happen is tourism will continue to fall, and economically, lovely Greece will feel the effects.'

 

[badger2]

In lieu of a vaccine, if the Chinese use chloroquine against COVID-19, there is chance of mutations against it. We have already mentioned the phosphorylation site in the study of Benvenuto et al (Rome, etc.) for COVID-19 (post #151).

Andes Hantavirus / Immunity-Regulating Virulence
An innate immunity-regulating virulence determinant is uniquely encoded by the Andes virus nucleocapsid protein. - PubMed - NCBI
'....ANDV is the only hantavirus known to spread from person to person and shown to cause highly lethal pulmonary syndrome (HPS) in patients and Syrian hamsters....phosphorylation of serine396.'

Pubmed search, 'chloroquine resistance amino acid' retrieves 271 references.

Aug 2019 Heidelberg, Strasbourg, Paris: Chloroquine Resistance Transporter Phosphomimetic Substitution
Phosphomimetic substitution at Ser-33 of the chloroquine resistance transporter PfCRT reconstitutes drug responses in Plasmodium falciparum. - PubMed - NCBI
'....serine33....increases transport velocity....'

Oct 2018 Thailand: Chloroquine Resistance Phenotype
Multiple Novel Mutations in Plasmodium falciparum Chloroquine Resistance Transporter Gene during Implementation of Artemisinin Combination Therapy ... - PubMed - NCBI
'....a point mutation at codon 76 (K76T)* is a key determinant of chloroquine resistance phenotype.'
* = lysine-to-threonine

We next attempt to link lysine-to-threonine (22 references):

Chikungunya Virus
Natural variation in the heparan sulfate binding domain of the eastern equine encephalitis virus E2 glycoprotein alters interactions with cell surf... - PubMed - NCBI
'....based on the recent chikungunya virus crystal structure...'

Obviously, we'll next attempt to link chikungunya as close as possible in space and time to the Lombardy COVID-19 cluster in Italy.

 

[badger2]

Chikungunya study (#491) is from Vaccine Research Center, University of Pittsburgh.

2016 Lombardy EXPO Area
Surveillance of Mosquitoes and Selected Arthropod-Borne Viruses in the Context of Milan EXPO 2015. - PubMed - NCBI
'....did not reveal the presence of chikungunya or dengue viruses in the local competent vectors inside the EXPO area.'

Jan 2020 Milan / Burkina Faso
The Use of Antimalarial Drugs against Viral Infection. - PubMed - NCBI

The COVID-19 bioweapon theory supposed inserted retroviral elements.

2019 Paris, France, Pavia, Italy / Endogenous Non-Retroviral Elements
Endogenous non-retroviral elements in genomes of Aedes mosquitoes and vector competence. - PubMed - NCBI

CHIKV Italy Outbreak, 2007
Modelling and Analyzing Virus Mutation Dynamics of Chikungunya Outbreaks. - PubMed - NCBI
'....La Reunion, Italy, China....In 2007, the disease was reported for the first time in Europe, causing a local outbreak in Northeastern Italy....our data fitting results show that the basic reproduction number in the 2007 Italy outbreak might be underestimated without considering the mutational dynamics....The co-existence of mutant and non-mutant CHIKV has been reported in this outbreak. We thus use our model to fit this outbreak data and investigate the role played by the mutational dynamics....in Castiglione di Cervia and Castiglione di Ravenna.'

Maps show proximities:

Lombardy
Lombardy - Wikipedia

Ravenna Province
Ravenna - Wikipedia

 

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23 Feb 2020 Coronavirus Did Not Originate in Wuhan Seafood Market
URL as found:
scmp.com/print/news/china/science/article/3051981/coronavirus-did-not-originate-wuhan-seafood-market-chinese

alternate URLs:
Coronavirus did not originate in Wuhan seafood market, scientists say

Coronavirus did not originate in Wuhan seafood market, scientists say
'....The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was instead imported from elsewhere, said researchers from Xishuangbanna Tropical Garden under the Chinese Academy of Sciences and the Chinese Institute for Brain Research....'

We first mentioned Xishuangbanna in post #398. This is the Type locality for the Type specimen of the Many-Banded Krait subspecies, Bungarus multicinctus wanghaotingi. The California Academy of Sciences describe B. m. wanghaotingi in post #366.

 

[badger2]

12 min ago: Dow Plunges
Dow plunges 900 points as coronavirus cases outside China jump

 

[badger2]

Deaths now at 2,628 (post #279).

Avian Flu Talk: Italy. There are 80 people hospitalized! 88 cases in Lombardy, 24 in Veneto, 6 in Piedmont, 9 in Emilia Romagna and 2 in Lazio (the pair of Chinese tourists). There are apparently armed roadblocks preventing people from leaving some towns. Lombardy, the region in Italy most badly affected, announced 53 new cases on Sunday night bringing the total there to 165 in only four days.'

 

[badger2]

It's not possible to URL link this video at Youtube: Italy Hunts Coronavirus Super Spreader
******************************************************************************************************
We investigate a pangolin connection retrieved by an automated prediction system for feline leukemia virus, a gammaretrovirus.

Predicted Manis javanica Feline Leukemia Virus
PREDICTED: Manis javanica feline leukemia virus subgroup C cellular re - Nucleotide - NCBI

There is a vaccine link:
Sequence 1 from Patent U.S. 4789702
Sequence 1 from Patent US 4789702 - Nucleotide - NCBI

We have already mentioned env insertions into coronavirus genomes in this thread. From a Japanese study we find an interesting mutation at least linking lysine (the lysine-to-threonine as key determinant of chloroquine resistance, previous posts):

Nov 2019 Japan / E148K FeLV Envelope
Tracking the Fate of Endogenous Retrovirus Segregation in Wild and Domestic Cats. - PubMed - NCBI
'....Introduction of the same mutation into feline and murine gammaretroviruses resulted in similar Env dysfunction.'

Homo sapiens LQK1 hypothetical protein long isoform (LQK1) mRNA, compl - Nucleotide - NCBI
'....H. sapiens LQK1....(and the Pubmed link on this page):
Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications an... - PubMed - NCBI
'....Diamond-Blackfan Anemia....'

 

[badger2]

This is a rare micro-RNA entry to further investigate:

May 2019 LQK1
Homo sapiens FLVCR1 divergent transcript (FLVCR1-DT), transcript varia - Nucleotide - NCBI
'....Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor....acts as MiR-513c sponge to modulate cancer cell proliferation, migration and invasion in hepatocellular carcinoma.'

'We have been investigating the aetiology of, and the possible relationships between leukaemia in man and domestic animals. We have shown that feline leukaemia (lymphosarcoma) is associated with a virus which has similar morphological and physical characteristics to the known leukaemogenic viruses of fowl and mouse. The feline leukaemia virus (FeLV) is found in the tissues of spontaneously diseased animals, and induces leukaemia in experimental cats inoculated shortly after birth. FeLV replicates in vitro, in cells explanted from leukaemic tissues, and in normal embryonic feline cells inoculated with cell-free extracts of tumours. WE have found that FeLV grows in human cells.
....
Fig. 1 An incomplete viral particle, showing the developing internal membrane structure, budding from the surface of a human lung cell, 29 days after infection with FeLV, x 120,000.

These results indicate that FeLV grows in human cells. As far as we are aware, this is the first time that a field strain of leukaemia virus has been found to replicate in cultured cells from a widely unrelated species. The ability of FeLV to cross species barriers in vitro raises the question of the relationship of the known leukaemogenic viruses to leukaemia in man and in other domestic animals from which no viruses have been isolated so far. Recently, FeLV has been found to induce lymphosarcoma in dogs; although no virus has been isolated from spontaneous leukaemias in the dog, FeLV was recovered from the induced cases (personal communication from C.G. Rickard). This result is interesting in the light o9f our findings that FeLV replicates also in canine cells in vitro.'
Jarret, Laird, Hay, University of Glasgow, Animal Leukaemia Research Unit, Bearsden, Glasgow
(Nature 224 91969): 1208)

 

[badger2]

Nature 224 (1969): 1208

linking lymphosarcoma (post # 497) to lopinavir:

Jan 2014 Japan / HIV-1 / Lopinavir / Lymphoma Apoptosis
HIV protease inhibitor Lopinavir induces apoptosis of primary effusion lymphoma cells via suppression of NF-κB pathway. - PubMed - NCBI

May 2011 Lopinavir-Ritonavir / Nasopharynx Lymphoma / Serine 824
Combination antiretroviral therapy as treatment for human immunodeficiency virus-associated mucosa-associated lymphoid tissue type lymphoma of the ... - PubMed - NCBI

linking chloroquine (post #475, etc.) to lymphoma:

May 2017 Stony Brook, New York / Chloroquine / Burkitt Lymphoma / Serine 824 / Epstein-Barr
https://www.ncbi.nlm. nih.gov/pubmed/28249048

linking pangolin to Epstein-Barr:

PREDICTED: Manis javanica Epstein-Barr virus induced 3 (EBI3), transcr - Nucleotide - NCBI

 

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Chloroquine triggers Epstein-Barr virus replication through phosphorylation of KAP1/TRIM28 in Burkitt lymphoma cells. - PubMed - NCBI

 

[badger2]

Whereas lopinavir suppresses NF-kappaB (post #498), the hepatitis B virus modulates the NF-kappaB pathway.