Moveable Feast Cafe 2021/01/26 … Open Thread

Ioan.

The trusted servant of a greater cause
never rewarded for a hard days work
still going on and on
living the hard days without end

There came a greater day
all strife came to an end
a bright shining light
a sudden change occurred

A shift in the winds
wars that had been lost to an unkown cause
everyone speeking abruptly all at once
talking exitedly the world at blissful peace

The trusted servant of a greater cause
not rewarded for the hard days work keep going
some day come a stranger disguised as a friend
everyone excited to join the pain again,
but the trusted servant of an old cafe.

“Joe Biden delivered remarks on racial equality on Tuesday.

Joe Biden: I believe we are in a battle for the soul of this nation. And the simple truth is our soul be troubled as long as systemic racism is allowed to persist. We can’t eliminate ‘zimply’ overnight. We can’t ‘eliminateverthing.’ But it’s corrosive, it’s destructive and it’s costly. It costs every American. Not just who felt the sting of racial injustice. We’re not just less of a – We’re not just a nation of morally deprived because of systemic racism. We’re also less prosperous. We’re less successful. We’re less secure.”

🤷‍♂️

This is America. Compilation of all riots.

https://fukkot.com/riots/americas-weirdest-riot-videos/2020:06:04-06:44:28-I-can-only-assume-Portland.mp4

https://fukkot.com/riots/all/

There’s a lot of future-thoughts Saturn, Jupiter, Sun and Mercury are dealing with this week, and
starting next Monday, even Venus will join the company. Future, because in Aquarius all heavenly players are dealing with general things, which are yet in the state of buds and burgeon.

Herr Schwab, from the WEF has picked with fine skill this week’s constellation for the current forum.

Look, what intensities he was able to convene his club under:

http://astromundanediary.blogspot.com/2021/01/two-left-wings-since-monday-creativity.html

I so love it when the left-youth-old fogey plutocrat coalition starts to eat itself: AOC objects? ya think!!!

https://www.zerohedge.com/markets/you-can-not-purchase-additional-shares-robinhood-reportedly-removed-shuts-down-buying

Well, those who make the rules, control the game… Now, how to kick gold loose?

Chinese study-potential alternative treatment of COVID-19.

These seeds not only enhance your immune system they head for COVID”s spike protein.

“36 peptides with high GI absorption, out of the 1593 peptides released from seed proteins, could bind to the binding or catalytic sites of the spike protein, main protease and papain-like protease of SARS-CoV-2, after GI digestion.”

Quinoa and pumpkin especially promising. I would use along with D3, vitamin C, Quercetin and Zinc.

Note…..
Researchers led by Ding, who heads a lab in UC Riverside’s Institute for Integrative Genome Biology, have discovered that, like plants and invertebrate animals, mammals use the RNA interference (RNAi) process to destroy viruses within their own cells.

Really long, read the pertinent.
https://www.sciencedirect.com/science/article/pii/S2667031320300166
Excerpt:
SARS-CoV-2 spike protein-, main protease- and
papain-like-protease-targeting peptides from seed proteins following
gastrointestinal digestion: An in silico study
Author links open overlay panelFai-ChuWongabJoe-HuiOngaTsun-ThaiChaiab
https://doi.org/10.1016/j.phyplu.2020.100016Get rights and content
Under a Creative Commons licenseopen access
Abstract
Background
The anti-COVID-19 potential of phytochemicals was investigated in
numerous studies, but efficacy of peptides released by seed proteins
upon gastrointestinal (GI) digestion is underexplored.

Purpose
This study investigated whether multi-target anti-COVID-19 peptides
could be released from edible seeds following GI digestion, by using
in silico and molecular docking approaches.

Methods
Nineteen seed storage proteins from Chenopodium quinoa (quinoa),
Sesamum indicum (sesame), Brassica napus (rape), Helianthus annuus
(sunflower) and Cucurbita maxima (pumpkin) seeds were subjected to in
silico GI digestion, in order to detect the released peptides with
high GI absorption that concurrently target the spike protein, main
protease and papain-like protease of SARS-CoV-2.

Results
Molecular docking study revealed that 36 peptides with high GI
absorption, out of the 1593 peptides released from seed proteins,
could bind to the binding or catalytic sites of the spike protein,
main protease and papain-like protease of SARS-CoV-2, after GI
digestion. Among the five seeds, quinoa was predicted to release the
largest number (27) of multi-target peptides. When compared with PIY
(Pro-Ile-Tyr), a high-GI-absorption fragment released from a potential
anti-COVID-19 peptide, pumpkin-derived peptide PW (Pro-Trp) could bind
more strongly to SARS-CoV-2 spike protein. PW was superior to some
previously reported anti-SARS-CoV-2 phytochemicals when binding
affinities towards the three viral targets were compared.

Conclusion
Edible seeds are a potential source of anti-COVID-19 peptides upon GI
digestion, hence they should be considered as an alternative to assist
in the treatment and management of COVID-19.

Introduction
The pandemic of the coronavirus disease 2019 (COVID-19), caused by a
novel pathogenic virus named as Severe Acute Respiratory Syndrome
Coronavirus type 2 (SARS-CoV-2), has escalated globally. The great
pandemic potential of SARS-CoV-2 could be attributed to its high
human-to-human transmissible efficiency (Zehra et al., 2020). Patients
affected by COVID-19 most commonly experience cough, runny nose, fever
and headache, although some suffer from serious complications such as
severe pneumonia, bronchitis, multi-organ failure, respiratory
illness, and even deaths (Zehra et al., 2020). SARS-CoV-2 is a
beta-coronavirus whose genome codes for four major structural
proteins, namely spike, envelope, membrane and nucleocapsid proteins,
as well as non-structural proteins, for instance the main protease
(Mpro) and papain-like protease (PLpro) (Zehra et al., 2020). The
interaction between the receptor-binding domain (RBD) of SARS-CoV-2
spike glycoproteins and human angiotensin converting enzyme 2 (hACE2)
facilitates the entry of viral particles into the host cell, which
precedes infection (Naqvi et al., 2020; Wang et al., 2020a; Yi et al.,
2020). Nine residues, Leu455, Phe456, Ser459, Gln474, Ala475, Phe486,
Phe490, Gln493 and Pro499 form the key binding sites on RBD that are
crucial for the affinity of SARS-CoV-2 spike glycoprotein RBD for
hACE2 (Yi et al., 2020). Blocking the binding of SARS-CoV-2 spike
glycoproteins to hACE2 is a promising approach towards the prevention
and/or treatment of COVID-19 (Yi et al., 2020). Besides, viral
proteases critical in genomic transcription and replication are
attractive targets for drug development against SARS-CoV-2 (Naqvi et
al., 2020). Following the release of the coronavirus genome into the
host cell, polyproteins are translated and subsequently cleaved by
Mpro (mediated by catalytic-dyad His41 and Cys145) and PLpro (mediated
by catalytic-triad Cys111, His272 and Asp286) to produce functional
proteins for folding and packaging of new virions which are essential
for viral replication (Naqvi et al., 2020). Thus, inhibition of Mpro
and PLpro catalytic activities could potentially suppress SARS-CoV-2
replication and the spread of infection. Notably, there is no cleavage
motif characteristic of SARS-CoV-2 proteases that occurs in the human
host. Hence Mpro and PLpro could serve as specific targets in the
formulation of inhibition strategies and pharmacological treatments
against SARS-CoV-2 (Ortega et al., 2020).

In response to the COVID-19 pandemic, there is a need to develop
countermeasures urgently. This has fueled current interest among
researchers to adopt molecular docking and other in silico approaches
to evaluate the potential of existing antiviral drugs and bioactive
natural products in targeting SARS-CoV-2 (Fakih, 2020). Molecular
docking has been widely exploited as structure-based drug discovery
tool owing to its quick, low-cost and precise prediction of the
biological activity and interactions of ligands with target molecules.
With this approach, information on the bond types, binding affinity
and interactions between two molecules can be predicted from the
best-matching conformation (Tao et al., 2020). To date, molecular
docking studies have identified some natural and synthetic inhibitors
that could potentially block the binding between SARS-CoV-2 and hACE2
and potentially inhibit the catalytic activities of SARS-CoV-2 Mpro
and PLpro, as presented in Tables S1–S6. Notwithstanding the
foregoing, studies focusing on food-derived and other natural
peptides, specifically those that could concurrently target the spike
glycoproteins, Mpro and PLpro of SARS-CoV-2 are scarce.

Food peptides exhibit diverse bioactivities, including antiviral
activity (Agarwal and Gabrani, 2020). The potential of food-derived
peptides in the development of nutraceuticals and functional foods is
well-recognized (Chai et al., 2017; Wong et al., 2020b). Peptides are
also preferred as therapeutic agents due to their higher specificity,
efficiency and biodegradability, as well as lower molecular weight and
toxicity (Haggag et al., 2018). Considering the aforementioned, in
this study, we investigated whether food-derived peptides could serve
as multi-target inhibitors against host cell entry and viral
replication of SARS-CoV-2. Specifically, we explored the potential
release of such multifunctional peptides from the seed storage
proteins of Cucurbita maxima L. (Cucurbitaceae) (pumpkin), Chenopodium
quinoa Willd. (Amaranthaceae) (quinoa), Brassica napus L.
(Brassicaceae) (rape), Helianthus annuus L. (Asteraceae) (sunflower)
and Sesamum indicum L. (Pedaliaceae) (sesame) seeds by using in silico
gastrointestinal (GI) digestion, followed by molecular docking
analysis. Seed storage proteins are the major proteins in the five
seeds and are likely to be the main sources of bioactive peptides upon
oral consumption and GI digestion. The nutritional values and the
bioactivity of peptides derived from the five seeds have been reported
(Bao et al., 2020; Guo et al., 2020; Han et al., 2019;
Innocent-Ukachi, 2019; Vilcacundo et al., 2018; Wang et al., 2020b).
Currently, there is still no effective approved treatment or vaccine
that can be used to tackle or prevent COVID-19. The outcome of this
research could relevant information that could be used by medical
professionals for formulating strategy to assist in the treatment
and/or management of COVID-19. Importantly, this research could serve
as the basis for future studies to elucidate the health-promoting
effects of seed peptides upon oral ingestion, especially in relation
to coronavirus diseases.

Methods
In silico GI digestion and screening for GI absorption
Nineteen seed storage proteins found in pumpkin, quinoa, rape,
sunflower and sesame seeds (Guo et al., 2020; Han et al., 2019), were
targeted in this study. Quinoa seed protein sequences were retrieved
from NCBI (https://www.ncbi.nlm.nih.gov) (Clark et al., 2015) on 5
August 2020. The protein sequences of the other four seeds were
downloaded from the UniProt web server (http://www.uniprot.org) (The
UniProt Consortium, 2019) on 5 August 2020. In silico GI digestion of
peptides and the screening of GI absorption were performed by using
BIOPEP-UWM (http://www.uwm.edu.pl/biochemia/index.php/en/biopep)
(Minkiewicz et al., 2019) and SwissADME (http://www.swissadme.ch)
(Daina et al., 2017) web servers, respectively, as previously
described (Wong et al., 2020a). Besides, phytochemicals used as
references in molecular docking studies were also screened for GI
absorption, entering their canonical Simplified Molecular-Input
Line-Entry System (SMILES) from PubChem
(https://pubchem.ncbi.nlm.nih.gov) (Kim et al., 2016) as input to be
analyzed by SwissADME. Following screening, peptides and reference
phytochemicals predicted to have high GI absorption (Tables S4–S6)
were taken for molecular docking analysis.

Molecular docking analyses with HPEPDOCK
The crystal structures of SARS-CoV-2 proteins were obtained from the
Protein Data Bank (http://www.rcsb.org/pdb) (Berman et al., 2000;
Burley et al., 2018). Three SARS-CoV-2 viral proteins were chosen for
this study, namely spike glycoprotein RBD (PDB ID: 6LZG)(Wang et al.,
2020a), Mpro (PDB ID: 6LU7) (Jin et al., 2020) and PLpro (PDB ID:
6W9C) (Osipiuk et al., 2020). Proteins and ligands were separated and
prepared for molecular docking by using BIOVIA Discovery Studio
Visualizer (BIOVIA, Dassault Systèmes, BIOVIA Discovery Studio
Visualizer, Version 20.1.0.192, San Diego: Dassault Systèmes, 2020),
as previously reported (Wong et al., 2020a). Crystallographic water
molecules were removed when the target protein structures were
prepared for molecular docking analysis. There is no evidence in the
literature that such water molecules are part of the viral proteins
structure and tightly bound to viral proteins. Hence, maintaining the
water molecules in the target protein structures for molecular docking
simulation is not justified.

To perform molecular docking on the HPEPDOCK server
(http://huanglab.phys.hust.edu.cn/hpepdock) (Zhou et al., 2018), the
three prepared viral proteins were uploaded as receptor inputs. The
prepared hACE2 and N3 were uploaded as binding site references for RBD
and Mpro respectively. For PLpro, three receptor binding residues
Cys111, His272 and Asp286 were entered in the docking option for
HPEPDOCK analysis (Wlodawer et al., 2020). High-GI-absorption seed
peptides released from in silico GI digestion and selected reference
peptides that were previously reported to bind to SARS-CoV-2 viral
proteins, where 3D structures are not available, were entered in the
FASTA format as peptide input. Tables S1–S3 list the reference
peptides used and sources of their crystal structures, where
available. The peptide model giving the lowest (most negative) docking
score as indicated by the HPEPDOCK analysis was chosen to combine with
the respective SARS-CoV-2 viral protein to form a docked model. The
protein-peptide interactions of the docked model were analyzed by
using LigPlot+ v.2.2 (Laskowski and Swindells, 2011; Wallace et al.,
1995). The binding poses of selected peptides on the surface of the
viral proteins were visualized by using BIOVIA Discovery Studio
Visualizer.

Molecular docking analyses with AutoDock Vina tool in PyRx
Following HPEPDOCK analysis, the high-GI-absorption seed peptide with
the lowest docking energy score when docked on three SARS-CoV-2 target
proteins was further compared with selected phytochemicals (Tables
S4–S6). The reference phytochemicals were chosen from those reported
to bind to the three viral proteins and also predicted in this study
to have high GI absorption. Molecular docking analysis of the selected
seed peptide and reference phytochemicals was performed by using the
AutoDock Vina option in PyRx 0.8 (Dallakyan and Olson, 2015; Trott and
Olson, 2010) as previously described (Wong et al., 2020a). Docking was
carried out for the spike protein RBD, with the grid box set to center
x-, y-, z-axis values of -40.34, 30.85, 6.61 with dimension of 35 Å x
50 Å x 30 Å, encompassing 21 binding site residues (Lys417, Gly446,
Tyr449, Tyr453, Leu455, Phe456, Tyr473, Ala475, Gly476, Glu484,
Phe486, Asn487, Tyr489, Phe490, Gln493, Gly496, Gln498, Thr500,
Asn501, Gly502 and Tyr505) (Wang et al., 2020a) and three other RBD
residues (Ser459, Gln474 and Pro499) reported to be important for
RBD-hACE2 binding (Yi et al., 2020). For Mpro, grid box was set with
center x-, y-, z-axis values of -10.71, 12.41, 68.83 with dimension of
15 Å x 25 Å x 15 Å, surrounding the catalytic-dyad His41 and Cys145
(Ortega et al., 2020). For the docking of PLpro, the grid box was set
with center x-, y-, z-axis values of -37.19, 24.28, 37.99 with each
dimension of 20 Å, encircling the catalytic-triad Cys111, His272 and
Asp286 (Wlodawer et al., 2020). The resultant binding affinities of
the peptide and reference phytochemicals were tabulated.

Data analysis
For binding affinities, data are presented as mean standard errors
based on analysis in triplicates. Statistical analysis was performed
by using the SAS University Edition Software (Version 9.4)
(https://www.sas.com/en_us/software/university-edition.html). P-value
of less than 0.05 was considered as statistically significant
according to Tukey’s test.

Results and discussion
In silico GI digestion generated a total of 1593 peptides fragments
from 19 seed storage proteins taken from the five seed samples. The
largest number of peptide fragments (801 fragments) were released from
quinoa seed storage proteins, whereas the smallest number of peptide
fragments (194 fragments) were from rape seed (Table 1). Regardless of
seed type, more peptide fragments were released from the globulin-type
proteins than from the albumin-type. For example, the 13S and 11S
globulins of the quinoa seed collectively released about 93% of all
GI-released peptide fragments. Our finding agrees with the observation
that most peptide fragments found in the gastroduodenal digest of
quinoa proteins were derived from 11S globulin of the seed (Vilcacundo
et al., 2018). The distribution of peptide length in the in silico GI
digestion-released fragments varied among the five seeds. For each
seed storage protein listed in Table 1, the total pool of 2- and
3-residue peptides accounts for about 27–50% of the total number of
peptides released. Such short peptides are of great interest as they
may be absorbed intact through the epithelium of GI tract, entering
the blood stream and producing biological effects at the tissue level
(Wang et al., 2019). Thus, our findings suggest the five seeds
analyzed in this study are likely to release a significant portion of
potentially bioavailable peptides upon GI digestion. Besides
resistance to GI digestion, GI absorption is another determinant of
the bioavailability of short peptides. As predicted by the SwissADME
tool, the greatest number of high-GI-absorption peptides was released
from quinoa (108 fragments), in contrast with the smallest number from
sunflower seeds. For all five seeds, the globulin-type seed storage
proteins are the main contributors of high-GI-absorption peptides
(Table 1). Together, our finding suggests that the quinoa seed, in
particular its globulin-type storage proteins, is a promising source
of potentially bioavailable peptides, which deserves more research
attention in future.

attn: Mundanomaniac ….a father who speaks for his children against school board’s hands off approach to education.

https://www.zerohedge.com/political/youre-bunch-cowards-va-parent-unloads-school-board-not-reopening-viral-video

… and I thought this was interesting (not to be read as an endorsement of Trump)

The Countries in Which Hydroxychloroquine Treatment of Covid Was Permitted Have a 79% Lower Covid Mortality Rate

“As I early reported, HCQ with zinc and azithromycin cures Covid. President Trump said so too. Big Pharma wanted to sell a vaccine. Their agent Dr. Fauci and the presstitutes who wanted yet another issue with which to attack Trump declared HCQ harmful. A couple of false studies got published and were used to block the use of HCQ. Consequently, many people died for the sake of presstitute criticism of President Trump.

Social media such as Facebook censored experts who reported HCQ’s effectiveness. Now the American Journal of Medicine has admitted that the evidence supports HCQ’s safety and effectiveness. Facebook admits it made a mistake, a mistake that contributed to the death of hundreds of thousands of people. Has the moron running Facebook learned the lesson that censorship is deadly?” – Dr PCR

https://www.thegatewaypundit.com/2021/01/440000-americans-dead-facebook-american-journal-medicine-admit-stand-hcq-wrong-people-prosecuted/

Regards

This could get interesting

15 hours ago EU orders RAIDS on AstraZeneca factory amid threat of UK Covid vaccine export ban

https://www.express.co.uk/news/politics/1390454/EU-covid-vaccine-row-uk-astrazeneca-factory-raided-belgium-uk-export-ban

Regards

Posted without comment:

https://www.rt.com/news/514056-china-anal-swabs-covid-video/