➡️ Cell reprogramming expressed through the RNA-induced mutagenicity of SARSCoV 2, of the infected cells. 👇
doi.org/10.5281/zenodo…
➡️The mechanism:
1)Cellular entry of SARS-CoV-2 depends on the binding of protein S to the angiotensin 2 converting enzyme (ACE2) which is a specific cellular receptor, located on the surface of the host cell, to facilitate zoonotic transfer (these viruses may involve ACE2 from
2) various animal species.)

Beta-coronaviruses replicate in the cytoplasm; Cellular compartments such as the endoplasmic reticulum and the intermediate compartment of the endoplasmic reticulum of the Golgi apparatus undergo intense remodeling.

After the internalization and
3) release of RNA, in the cytoplasm, a set of proteins is synthesized triggering the formation of vesicles which become a viral platform ensuring efficient RNA replication and transcription.

The new coronavirus particles are assembled in the endoplasmic reticulum and the Golgi
4) complex.

Membrane budding between these compartments has been reported in association with N protein and genomic RNA along with M, E and S proteins.

Complete virions are sent to the extracellular environment following a conventional "secretory pathway".
5) Coronavirus infection leads to massive remodeling of cell membranes; the proposed mechanism for virus export into the extracellular space is through the fusion of the transport compartment membrane with the cell plasma membrane.

The viral particles adhered to cell
6) surface protrusions which were shown to connect two cells.

It is assumed that this mechanism allows the virus to penetrate mucosal surfaces in vivo showing cells rich in microvilli.

Actin filaments play a vital role in cell viral extrusion for both RNA and DNA viruses.
7) Actin offers the power to discharge virus particles from the cytoskeleton network onto the surface of the filopodic bumps, allowing them to sprout on the surface.

Thus, for example, the communication between the two cells is made possible through thin filaments of F-actin
8)containing nanotube tunnels (filopodic protuberances)with dimensions of<0.7µm.

These intercellular membranous connections can provide the transfer of molecular information (viral particles).

This infectious spread of SARSCoV2,from cell to cell,is called:vira"cell navigation"
9) Once the cell induction mechanism has been explained, through SARS CoV 2 infection, the phosphorylation process produced by the kinase is explained.

Excessive kinase activity causes cells to grow out of control and can lead to cancer.

Among the many roles of kinase,
10) there is an increased phosphorylation of cytoskeletal protein targets such as en-catenin (CTNNA1 S641) and the heavy chain of the motor protein Myosin, Ia (MYH9 S1943).

CK2 and N, co-localize virus-induced joint protrusions.
11) Phosphoproteomic data indicated the regulation of different Chinase and Effector proteins, related to the cytoskeletal organization of infected cells, following the infectious action of SARS CoV 2.

The interaction of the  Nsp7 protein, with RHOA, may
12) contribute to downregulation.

On the contrary, signaling, via CK2, is strongly upregulated, as determined by the increase in phosphorylation of the infected sites.

In addition to these kinase-mediated effects, the SARS CoV 2 protein Nsp2 also interacts
13) directly with Strumpellin
(WASHC5), a subunit of the WASH complex that induces actin assembly, implying further regulation of the cytoskeleton during infection.

To investigate the relevance of these observations in a human infection model, high-resolution
14) immunofluorescence imaging of fixed Caco-2 human colonic epithelial cells was performed 24 hours after infection with SARS CoV 2, revealing a cluster of prominent M proteins, marked by assembled SARS CoV 2 viral particles, located along the
15) protrusions, and on the tips, rich in phylopoidal actin.

SARS-CoV-2 infection induced a dramatic increase in filopodic protrusions, which were significantly longer and branched than in uninfected cells.

The reorganization of the actin cytoskeleton is a common feature
16) cytoskeleton is a common feature of many viral infections and is associated with different phases of the viral life cycle; the SARS CoV 2 virus, contained within the cytoskeleton, is then released and / or diffused, from cell to cell, within the epithelial monolayers.
17) So since Rho / PAK / ROCK are downregulated, we wondered if CK2 could play a role in this process.

Indeed,at 24 hours after the trial, the infected cells showed the expression of CK2 along the thin filopodial protrusions, partially co-localized with the SARS CoV 2 N protein.
18) Scanning electron microscopy was used to view cell protrusions at a higher resolution.

The assembled viral particles are clearly visible along these philopoidal protuberances, inducing their shape and direction.

Finally, a global phosphoproteomic analysis of
19) phosphoproteomic analysis of Vero E6 cells, which overexpress the N protein, was performed and the significantly upregulated activity of CK2 was confirmed.

Since the activity of CK2 can promote the polymerization of Actin, it is consequential that the
20) protein N can also control the CK2 activity and regulate the organization of the cytoskeleton.

Scientists found that CK2 pharmacological inhibitors (silmitasertib) possess strong antiviral efficacy.

It was found that Silmitasertib is an inhibitor of  CSNK2A1 and
21) CSNK2A2, in fact it has antiviral activity (IC 50 = 2.34 μM) and
has a potential role in the remodeling of the extracellular matrix in case of SARS-CoV-2 infection.

CONCLUSION:
Scientists found that the on / off switches changed significantly in 40 of the 332 proteins that
22) interact with SARS CoV 2.

The changes occur because the virus makes or composes 49 enzymes called kinases.

The upward or downward composition of kinases causes them to alter these 40 proteins that interact with the virus.

Kinases are like "guards" who
23) protect our health until the new coronavirus changes them, turning them against us.

In any case, the new study has identified pharmacological treatments that can prevent the virus from transforming "guards" into "aggressors".

The virus overwhelmingly hijacks
24) a kinase called CK2, which plays a key role in the basic structure of the cell, as well as in its growth, proliferation and death.

Tests found that this new drug, called Silmitasertib, inhibits CK2 and eliminates the new coronavirus.👇

linkinghub.elsevier.com/retrieve/pii/S…
25) THE FINAL:
In conclusion, the development in the laboratory of an RNA virus of the scope of SARS CoV 2 turns out to be of a truly enormous complexity.

In Whuan there are 3 Departments, all of which are part of the Pla: the Department of Zootechnics, the Department of
26) Agriculture, and the Department of Biology, which collaborate in the development of integrated projects which are then headed by WIW.

To be able to make a highly infectious virus air, it is necessary to create an extremely volatile air vector, capable of even passing
27) through the cracks of a watertight, closed door of a Laboratory (as happened at Whuan's BSL4).

The virus that lends itself well is Adenovirus (type Ad5); there are 7 human adenovirus species and 57 serotypes.

Adenoviruses are commonly acquired following contact with
28) the secretions of an infected person (including transmission through the hands) or with a contaminated object.
The infection can be airborne or waterborne.
Shedding of the virus by patients with asymptomatic respiratory, or gastrointestinal, infection can
29) continue for months, or even years.

Once the passage from the Bats clade (with a highly pathogenic infectivity) to the human clade has been resolved, through recombination, in-vitro and in-vivo, of the virus, with the use of intermediate animals, in ACE2,
30) with a high charge ORF and humanized, leukemicized mice, which allow passage into human cells.

The PLA scientists have discovered that the regulator, which allows high infectivity in human cells, is the Kinase and more precisely the activity ratio between CSNK2A1 and CK2.
31) It has been shown, from molecular microscopy studies, that RNA, expressed by SARS CoV 2 in the cell, induces overexpression protein N, which upregulates CK2 activity; since the activity of CK2 can favor the polymerization of Actin and regulate both the
32) filopodic protusion (writing for the remodeling of the extracellular matrix), and the organization of the cellular cytoskeleton itself.

➡️ Recent studies on the interaction of SARS CoV 2 on the cytoskeleton of the cell membrane, and on its induced
33)reprogramming, have found that the relationship between CSNK2A1 (Casein Kinase 2 alpha 1) and CK2 is a determining factor in the massive reproduction of the virus in the body human, as happened also for HIV 1.

Therefore CSNK2A1 regulates the activity of CK2 (Beta CK2) which,
34) by phosphorylating with B23, would activate both the replication of SARS CoV 2 and the replication of HIV-1.

➡️ CSNK2A1 regulates the cell cycle and its apoptosis (programmed cell death).

➡️ CK2 upregulates massive cell production.

➡️ Inhibition of CK2, with
35) Silmitasertib,regulates the promotion of programmed cell death.

ncbi.nlm.nih.gov/gene/1457

proteinatlas.org/ENSG0000010126…

m.ensembl.org/Homo_sapiens/G…

➡️ CSNK2A1 transgenic mice (casein kinase 2,polypeptide alpha 1) in Mus Musculus.

informatics.jax.org/marker/MGI:885…

ncbi.nlm.nih.gov/gene/12995

END
➡️ 1) The development, in the laboratory, of an RNA virus, of the type of SARS CoV 2, turns out to be very complex.

In Whuan there are 3 Departments, all of which are part of the Pla: the Department of Zootechnics, the Department of Agriculture and the Department of
2) Biology, which then collaborate in the development of integrated projects directed by WIW. In order to make aerial a highly contagious virus, it is necessary to create an aerial vector, extremely volatile, able to pass also through the cracks of a laboratory watertight
3) door (as happened at Whuan's BSL4). The virus that lends itself well is an Adenovirus (type Ad5); there are 7 human adenovirus species and 57 serotypes. Adenoviruses are commonly acquired following contact with secretions from an infected person (including transmission
4) through the hands) or with a contaminated object.

The infection can be transmitted by air or water.

The spread of the virus by patients with asymptomatic respiratory or gastrointestinal infection can continue for months, or even years.
5) Once the passage from the bat clade (with high pathogenic infectivity) to the human clade has been resolved, through recombination, in vitro and in vivo, of the virus, with the use of intermediate animals, in ACE2, with high ORF charge and humanized mice and leukemic, it
6) is possible to obtain the passage into human cells.

The PLA scientists discovered that the regulator,which enables high infectivity in human cells, is kinase and more precisely the activity ratio between CSNK2A1 and CK2.

It has been shown,from molecular microscopy studies,
7) that the RNA, expressed by SARS CoV 2 in the cell, induces the over-expressed N protein, which upregulates the activity of CK2; since the activity of CK2 can favor the polymerization of Actin and then also regulate both the filopodic protusion (writing for the
8) remodeling of the extracellular matrix), and the organization of the cellular cytoskeleton itself.

Recent studies on the interaction of SARS CoV 2 with the cytoskeleton of the cell membrane, and on its induced reprogramming, have found that the relationship between
9) CSNK2A1 (Casein kinase 2 alpha 1) and CK2 is a determining factor in the massive reproduction of this chimeric virus in the human organism, as was also the case for HIV 1.
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More from @BidoliNicola

6 Apr
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➡️ Unexpected discovery of multiple coronaviruses and a BSL-3 pathogen in agricultural cotton and rice sequencing dataset.

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👇
ncbi.nlm.nih.gov/Taxonomy/Brows…

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👇
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➡️ Cell reprogramming expressed through RNA-induced mutagenicity of #SARSCoV2 in infected cells confirmed.👇

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Read 47 tweets
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@Grace42Thorn @janieyaya @MartinaSisters ➡️1) Probable, not all retroviruses cause cancer, but all RNA tumor viruses are retroviruses.
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