Implications for Possible Consequences of COVID-19 Vaccines

md_a

Member
Joined
Aug 31, 2015
Messages
468

Abstract​

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses its spike protein to enter the host cells. Vaccines that introduce the spike protein into our body to elicit virus-neutralizing antibodies are currently being developed. In this article, we note that human host cells sensitively respond to the spike protein to elicit cell signaling. Thus, it is important to be aware that the spike protein produced by the new COVID-19 vaccines may also affect the host cells. We should monitor the long-term consequences of these vaccines carefully, especially when they are administered to otherwise healthy individuals. Further investigations on the effects of the SARS-CoV-2 spike protein on human cells and appropriate experimental animal models are warranted.
Keywords: cell signaling; coronavirus; COVID-19; SARS-CoV-2; spike protein; vaccine

1. Introduction​

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense, single-stranded RNA virus [1,2]. As of the end of December 2020, over 80 million people have been infected with SARS-CoV-2, causing 1.8 million deaths worldwide. SARS-CoV-2 uses its viral membrane fusion protein, known as a spike protein, to bind to angiotensin converting enzyme 2 (ACE2) as a ‘receptor’ in order to enter human host cells [3,4], causing severe pneumonia and acute respiratory distress syndrome (ARDS) [5]. Elderly patients with cardiovascular disease are particularly susceptible to developing serious COVID-19 conditions that in some cases lead to death, while young and healthy individuals are largely resistant to developing severe symptoms [1,6,7]. As COVID-19 continues to cause serious health, economic, and sociological problems, the world awaits the widespread rollout of effective vaccines that may end this pandemic.
The SARS-CoV-2 spike protein, a class I viral fusion protein, is critical to initiating the interactions between the virus and the host cell surface receptor, facilitating viral entry into the host cell by assisting in the fusion of the viral and host cell membranes. This protein consists of two subunits: Subunit 1 (S1) that contains the ACE2 receptor-binding domain (RBD) and Subunit 2 (S2) that plays a role in the fusion process [3,4] (Figure 1). The SARS-CoV-2 spike protein is the major target for the development of COVID-19 vaccines.
Vaccines 09 00036 g001 550

Figure 1. Structure of SARS-CoV-2 spike protein. The spike protein consists of Subunit 1 (S1) and Subunit 2 (S2). The S1 subunit contains the receptor-binding domain (RBD) that binds to ACE2 of the host cell membrane. The S2 subunit is responsible for fusion. In our previous study described in Section 3 and Section 5, we used full-length S1 (Val16-Gln690) depicted with blue and red regions and the RBD only-containing protein (Arg319-Phe541) shown in red of the SARS-CoV-2 spike protein (GenBank Accession Number: QHD43416.1).

2. Development of Spike Protein-Based COVID-19 Vaccines​

The remarkably rapid development of vaccines and therapeutics for COVID-19 in 2020 has been due to effective collaborations between governments and the private sector. On 9 November 2020, Pfizer and BioNTech announced that their mRNA-based vaccine candidate, BNT162b2, is more than 90% effective against COVID-19 [8]. This was welcome news in that it revealed that effective vaccines may soon become available. BNT162b2 encodes the SARS-CoV-2 spike protein to elicit virus-neutralizing antibodies [9,10]. More specifically, it encodes the full-length spike protein of SARS-CoV-2 with two amino acids mutated to proline in the S2 subunit to maintain the prefusion conformation, while its sister vaccine BNT162b1 (also from Pfizer/BioNTech) encodes only the RBD of the SARS-CoV-2 spike protein, trimerized by the addition of a T4 fibritin foldon domain [9,10,11]. Clinical trials have demonstrated that neither BNT162b1 [11] nor BNT162b12 [9,10] exhibit serious short-term adverse effects. On 10 December 2020, the results of a large clinical trial for BNT162b were published, showing that this vaccine conferred 95% protection in persons 16 years of age or older [12]. Long-term consequences of these vaccines are, however, unknown.
Another promising vaccine, mRNA-1273 by Moderna, is also an RNA vaccine that encodes the full-length SARS-CoV-2 spike protein [13]. Viral vector-based vaccines such as AZD1222 by AstraZeneca, which uses a non-replicating chimpanzee adenovirus vector [14], Ad26.COV2.S by Johnson & Johnson, a non-replicating adenovirus 26-based system [15], and Gam-COVID-Vac (Sputnik V) by Gamaleya Research Institute of Epidemiology and Microbiology [16], all express the SARS-CoV-2 spike protein. NVX-CoV2373 (Novavax), a recombinant protein-based vaccine [17], is also the full-length SARS-CoV-2 spike protein. These vaccines as well as many others under development [18,19,20] introduce the SARS-CoV-2 spike protein into our body, so that the production of antibodies and immunity against SARS-CoV-2 are stimulated.

3. SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Cells​

It was found that the treatment of cultured primary human pulmonary artery smooth muscle cells (SMCs) or human pulmonary artery endothelial cells with the recombinant SARS-CoV-2 spike protein S1 subunit is sufficient to promote cell signaling without the rest of the viral components [21]. Furthermore, our analysis of the postmortem lung tissues of patients who died of COVID-19 has determined that these patients exhibited pulmonary vascular wall thickening, a hallmark of pulmonary arterial hypertension (PAH) [21]. Based on these results, we proposed that the SARS-CoV-2 spike protein (without the rest of the viral components) triggers cell signaling events that may promote pulmonary vascular remodeling and PAH as well as possibly other cardiovascular complications [21,22].
In our cell culture experiments, two recombinant SARS-CoV-2 spike proteins, both of which contain the RBD, were studied [21]. The full-length S1 subunit protein contains most of the S1 subunit (Val16–Gln690), while the RBD S1 subunit protein only contains the RBD region (Arg319–Phe541), as shown in Figure 1. Cultured primary human pulmonary artery SMCs and human pulmonary artery endothelial cells were treated with these proteins for 10 min. We found, using the phospho-specific MEK antibody, that the recombinant full-length S1 subunit of SARS-CoV-2 alone at a concentration as low as 130 pM activated MEK, the activator of extracellular signal-regulated kinase (ERK) and a well-known signal transduction mechanism for cell growth [23]. By contrast, such activation of cell signaling by the spike protein did not occur in rat pulmonary artery SMCs [21].
While ACE2 is now well known as a ‘receptor’ to which the SARS-CoV-2 spike protein binds on human host cells in order to facilitate the membrane fusion and gain viral entry, the usual physiological function of ACE2 is not to serve as a membrane receptor to transduce intracellular signals. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving angiotensin II to angiotensin (1–7) and regulating blood pressure [24,25] (Figure 2). However, ten years ago, Chen et al. [26] reported the intriguing findings showing that ACE2 acts as a membrane receptor for cell signal transduction in response to the spike protein of SARS-CoV (now also known as SARS-CoV-1, the virus that caused the SARS outbreak in 2002–2004) in the human lung alveolar epithelial cell line, A549. The spike protein of SARS-CoV-1 is 76–78% identical to that of SARS-CoV-2 [27]. In their study, it was shown that the binding of the full-length spike protein to ACE2 triggered the casein kinase II-dependent activation of activator protein-1 (AP-1) transcription factor and subsequent gene transcriptional events [26]. Their finding on SARS-CoV-1 [26] and ours on SARS-CoV-2 [21] indicate that the spike protein remarkably functionally converts ACE2 (that is normally a peptidase enzyme) into a membrane receptor for cell signaling that uses the spike protein as a ligand for its activation (Figure 2).
Vaccines 09 00036 g002 550

Figure 2. Biological functions of ACE2. In physiological situations, ACE2 functions as a carboxypeptidase enzyme that catalyzes the hydrolysis of angiotensin II (Ang II) into Ang(1–7) by cleaving off a phenylalanine (Phe). In the presence of the spike protein, this enzyme becomes a membrane receptor for cell signaling that uses the spike protein as a ligand for its activation.
Kuba et al. [28] showed that the injection of mice with recombinant SARS-CoV-1 spike protein reduced the ACE2 expression and worsened the acid-induced lung injury. In mice with an acid-induced lung injury, the recombinant SARS-CoV-1 spike protein dramatically increased angiotensin II, and the angiotensin receptor inhibitor losartan attenuated the spike protein-induced enhancement of lung injury [28]. Thus, these in vivo studies demonstrated that the spike protein of SARS-CoV-1 (without the rest of the virus) reduces the ACE2 expression, increases the level of angiotensin II, and exacerbates the lung injury.
The SARS-CoV-2 spike protein without the rest of the viral components has also been shown to activate cell signaling by Patra et al. [29]. The authors reported that the full-length SARS-CoV-2 spike protein expressed by the means of transient transfection, either in the human lung alveolar epithelial cell line A549 or in the human liver epithelial cell line Huh7.5, activated NF-κB and AP-1 transcription factors as well as p38 and ERK mitogen-activated protein kinases, releasing interleukin-6. This cell signaling cascade was found to be triggered by the SARS-CoV-2 spike protein downregulating the ACE2 protein expression, subsequently activating the angiotensin II type 1 receptor [29]. These experiments using transient transfection may reflect the intracellular effects of the spike protein that could be triggered by the RNA- and viral vector-based vaccines.
These results collectively reinforce the idea that human cells are sensitively affected by the extracellular and/or intracellular spike proteins though the activation of cell signal transduction.

4. Pulmonary Hypertension​

PAH is a serious disease without a cure that can affect males and females of any age including children. The increased pulmonary vascular resistance in PAH results in right heart failure and subsequently death. Patients diagnosed with PAH only live for 2–3 years from the time of diagnosis on average if untreated [30,31]. Even with currently available therapies, only 60–70% of PAH patients survive for three years [32,33,34,35]. PAH is hard to detect because its symptoms (e.g., shortness of breath, fatigue, and dizziness) are similar to those of other common non-life threatening conditions, and the official diagnosis for PAH must be made through invasive right heart catheterization [36]. Endothelial dysfunction is a common feature of patients with PAH and COVID-19 [37,38].
PAH “outbreaks” have occurred in association with exposure to certain drugs or toxins [39]. A major outbreak of PAH occurred in 1965 and was associated with aminorex, a weight-loss stimulating drug [39,40]. Approximately 0.2% of people who took this drug developed PAH [40]. An epidemic was observed two years after the introduction of aminorex, and half of the patients died 10 years after the epidemic [39].
We studied pulmonary vessels of COVID-19 patients and those of H1N1 influenza-infected patients who died of ARDS [21]. The pulmonary arteries of postmortem COVID-19 patient lungs consistently exhibited histological characteristics of vascular wall thickening, mainly due to the hypertrophy of the tunica media. Detailed pathological analysis revealed that the boundaries between the vessels and the surrounding lung parenchyma have lost clarity, the SMCs of the middle lining of the arteries have enlarged, the nuclei of SMCs have swollen, and vacuoles have been generated in the cytoplasm of SMCs [21]. A morphometric analysis determined that the median pulmonary vascular wall thickness values were 15.4 μm for the COVID-19 patients and 6.7 μm for the influenza patients, and these values were significantly different from each other [21]. Pulmonary vascular wall thickening in COVID-19 patients was also observed on the computed tomography scan of the chest [41,42]. Thus, these results together indicated that COVID-19 is associated with pulmonary vascular wall thickening. Investigations on whether this pulmonary vascular wall thickening is related to clinically significant PAH and the role of the spike protein in the pathogenesis of PAH are warranted.

5. RBD Only-Containing SARS-CoV-2 Spike Protein Does Not Elicit Cell Signaling in Human Cells​

In contrast to the full-length spike protein [26,29] or the full-length SARS-CoV-2 spike protein S1 subunit [21], we found that the RBD only-containing protein (Figure 1) did not promote cell signaling. Our Western blotting results monitoring the MEK activation showed that the mean ± SEM phosphorylated MEK to MEK protein ratio values were 0.05 ± 0.003 (untreated), 1.9 ± 0.07 (treated with the full-length S1 protein), and 0.05 ± 0.003 (treated with the RBD only-containing protein) for human pulmonary artery SMCs; and 0.09 ± 0.006 (untreated), 0.90 ± 0.06 (treated with the full-length S1 protein), and 0.10 ± 0.003 (treated with the RBD only-containing protein) for human pulmonary artery endothelial cells [21].
The different effects of the full-length S1 and RBD only-containing proteins may be important considering that BNT162b2 and many other COVID-19 vaccines express the full-length spike protein, while the BNT162b1 vaccine encodes only the RBD region [9,10,11,12,13,14,15,16,17,18,19,20]. There are some other RBD-based COVID-19 vaccines being developed as well [43]. It is possible that the RBD-based vaccines are less immunogenic, but may not affect the host cells. Thus, they may be less risky considering potential long-term adverse effects. However, in the in vivo study of the SARS-CoV-1 spike protein described above [28], a deletion mutant that only contained the RBD also worsened the acid-induced lung failure, like the full-length spike protein. Thus, further work is needed to understand effects of the full-length spike protein and the RBD-only containing protein in various biological processes.

6. Discussion​

It is generally thought that the sole function of viral membrane fusion proteins is to allow the viruses to bind to the host cells for the purpose of viral entry into the cells, so that the genetic materials can be released and the viral replication and amplification can take place. However, recent observations suggest that the SARS-CoV-2 spike protein can by itself trigger cell signaling that can lead to various biological processes. It is reasonable to assume that such events, in some cases, result in the pathogenesis of certain diseases.
Our laboratory only tested the effects of the SARS-CoV-2 spike protein in lung vascular cells and those implicated in the development of PAH. However, this protein may also affect the cells of systemic and coronary vasculatures, eliciting other cardiovascular diseases such as coronary artery disease, systemic hypertension, and stroke. In addition to cardiovascular cells, other cells that express ACE2 have the potential to be affected by the SARS-CoV-2 spike protein, which may cause adverse pathological events. Thus, it is important to consider the possibility that the SARS-CoV-2 spike protein produced by the new COVID-19 vaccines triggers cell signaling events that promote PAH, other cardiovascular complications, and/or complications in other tissues/organs in certain individuals (Figure 3). We will need to monitor carefully the long-term consequences of COVID-19 vaccines that introduce the spike protein into the human body. Furthermore, while human data on the possible long-term consequences of spike protein-based COVID-19 vaccines will not be available soon, it is imperative that appropriate experimental animal models are employed as soon as possible to ensure that the SARS-CoV-2 spike protein does not elicit any signs of the pathogenesis of PAH or any other chronic pathological conditions.
Vaccines 09 00036 g003 550

Figure 3. Possible actions of the SARS-CoV-2 spike protein. The SARS-CoV-2 spike protein of the intact virus targets ACE2 of the host cells to facilitate the membrane fusion and the viral entry. The SARS-CoV-2 spike protein also elicits cell signaling in human cells [21,29]. COVID-19 vaccines introduce the spike protein into the human body. In addition to eliciting an immune response that suppresses the viral entry, the spike protein produced by the COVID-19 vaccines may also affect the host cells, possibly triggering adverse events. Further investigations addressing this possibility are warranted.

7. Conclusions​

In conclusion, the recent advancement in the SARS-CoV-2 spike protein-based COVID-19 vaccine development is exciting and has shed light on how to end the current pandemic. These vaccines should benefit elderly people with underlying conditions if they do not exhibit any acute adverse events. However, we need to consider their long-term consequences carefully, especially when they are administered to otherwise healthy individuals as well as young adults and children. In addition to evaluating data that will become available from SARS-CoV-2 infected individuals as well as those who received the spike protein-based vaccines, further investigations of the effects of the SARS-CoV-2 spike protein in human cells and appropriate animal models are warranted.

 

Blossom

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Joined
Nov 23, 2013
Messages
11,033
Location
Indiana USA

Abstract​

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 uses its spike protein to enter the host cells. Vaccines that introduce the spike protein into our body to elicit virus-neutralizing antibodies are currently being developed. In this article, we note that human host cells sensitively respond to the spike protein to elicit cell signaling. Thus, it is important to be aware that the spike protein produced by the new COVID-19 vaccines may also affect the host cells. We should monitor the long-term consequences of these vaccines carefully, especially when they are administered to otherwise healthy individuals. Further investigations on the effects of the SARS-CoV-2 spike protein on human cells and appropriate experimental animal models are warranted.
Keywords: cell signaling; coronavirus; COVID-19; SARS-CoV-2; spike protein; vaccine

1. Introduction​

The world is suffering from the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense, single-stranded RNA virus [1,2]. As of the end of December 2020, over 80 million people have been infected with SARS-CoV-2, causing 1.8 million deaths worldwide. SARS-CoV-2 uses its viral membrane fusion protein, known as a spike protein, to bind to angiotensin converting enzyme 2 (ACE2) as a ‘receptor’ in order to enter human host cells [3,4], causing severe pneumonia and acute respiratory distress syndrome (ARDS) [5]. Elderly patients with cardiovascular disease are particularly susceptible to developing serious COVID-19 conditions that in some cases lead to death, while young and healthy individuals are largely resistant to developing severe symptoms [1,6,7]. As COVID-19 continues to cause serious health, economic, and sociological problems, the world awaits the widespread rollout of effective vaccines that may end this pandemic.
The SARS-CoV-2 spike protein, a class I viral fusion protein, is critical to initiating the interactions between the virus and the host cell surface receptor, facilitating viral entry into the host cell by assisting in the fusion of the viral and host cell membranes. This protein consists of two subunits: Subunit 1 (S1) that contains the ACE2 receptor-binding domain (RBD) and Subunit 2 (S2) that plays a role in the fusion process [3,4] (Figure 1). The SARS-CoV-2 spike protein is the major target for the development of COVID-19 vaccines.
Vaccines 09 00036 g001 550

Figure 1. Structure of SARS-CoV-2 spike protein. The spike protein consists of Subunit 1 (S1) and Subunit 2 (S2). The S1 subunit contains the receptor-binding domain (RBD) that binds to ACE2 of the host cell membrane. The S2 subunit is responsible for fusion. In our previous study described in Section 3 and Section 5, we used full-length S1 (Val16-Gln690) depicted with blue and red regions and the RBD only-containing protein (Arg319-Phe541) shown in red of the SARS-CoV-2 spike protein (GenBank Accession Number: QHD43416.1).

2. Development of Spike Protein-Based COVID-19 Vaccines​

The remarkably rapid development of vaccines and therapeutics for COVID-19 in 2020 has been due to effective collaborations between governments and the private sector. On 9 November 2020, Pfizer and BioNTech announced that their mRNA-based vaccine candidate, BNT162b2, is more than 90% effective against COVID-19 [8]. This was welcome news in that it revealed that effective vaccines may soon become available. BNT162b2 encodes the SARS-CoV-2 spike protein to elicit virus-neutralizing antibodies [9,10]. More specifically, it encodes the full-length spike protein of SARS-CoV-2 with two amino acids mutated to proline in the S2 subunit to maintain the prefusion conformation, while its sister vaccine BNT162b1 (also from Pfizer/BioNTech) encodes only the RBD of the SARS-CoV-2 spike protein, trimerized by the addition of a T4 fibritin foldon domain [9,10,11]. Clinical trials have demonstrated that neither BNT162b1 [11] nor BNT162b12 [9,10] exhibit serious short-term adverse effects. On 10 December 2020, the results of a large clinical trial for BNT162b were published, showing that this vaccine conferred 95% protection in persons 16 years of age or older [12]. Long-term consequences of these vaccines are, however, unknown.
Another promising vaccine, mRNA-1273 by Moderna, is also an RNA vaccine that encodes the full-length SARS-CoV-2 spike protein [13]. Viral vector-based vaccines such as AZD1222 by AstraZeneca, which uses a non-replicating chimpanzee adenovirus vector [14], Ad26.COV2.S by Johnson & Johnson, a non-replicating adenovirus 26-based system [15], and Gam-COVID-Vac (Sputnik V) by Gamaleya Research Institute of Epidemiology and Microbiology [16], all express the SARS-CoV-2 spike protein. NVX-CoV2373 (Novavax), a recombinant protein-based vaccine [17], is also the full-length SARS-CoV-2 spike protein. These vaccines as well as many others under development [18,19,20] introduce the SARS-CoV-2 spike protein into our body, so that the production of antibodies and immunity against SARS-CoV-2 are stimulated.

3. SARS-CoV-2 Spike Protein Elicits Cell Signaling in Human Cells​

It was found that the treatment of cultured primary human pulmonary artery smooth muscle cells (SMCs) or human pulmonary artery endothelial cells with the recombinant SARS-CoV-2 spike protein S1 subunit is sufficient to promote cell signaling without the rest of the viral components [21]. Furthermore, our analysis of the postmortem lung tissues of patients who died of COVID-19 has determined that these patients exhibited pulmonary vascular wall thickening, a hallmark of pulmonary arterial hypertension (PAH) [21]. Based on these results, we proposed that the SARS-CoV-2 spike protein (without the rest of the viral components) triggers cell signaling events that may promote pulmonary vascular remodeling and PAH as well as possibly other cardiovascular complications [21,22].
In our cell culture experiments, two recombinant SARS-CoV-2 spike proteins, both of which contain the RBD, were studied [21]. The full-length S1 subunit protein contains most of the S1 subunit (Val16–Gln690), while the RBD S1 subunit protein only contains the RBD region (Arg319–Phe541), as shown in Figure 1. Cultured primary human pulmonary artery SMCs and human pulmonary artery endothelial cells were treated with these proteins for 10 min. We found, using the phospho-specific MEK antibody, that the recombinant full-length S1 subunit of SARS-CoV-2 alone at a concentration as low as 130 pM activated MEK, the activator of extracellular signal-regulated kinase (ERK) and a well-known signal transduction mechanism for cell growth [23]. By contrast, such activation of cell signaling by the spike protein did not occur in rat pulmonary artery SMCs [21].
While ACE2 is now well known as a ‘receptor’ to which the SARS-CoV-2 spike protein binds on human host cells in order to facilitate the membrane fusion and gain viral entry, the usual physiological function of ACE2 is not to serve as a membrane receptor to transduce intracellular signals. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving angiotensin II to angiotensin (1–7) and regulating blood pressure [24,25] (Figure 2). However, ten years ago, Chen et al. [26] reported the intriguing findings showing that ACE2 acts as a membrane receptor for cell signal transduction in response to the spike protein of SARS-CoV (now also known as SARS-CoV-1, the virus that caused the SARS outbreak in 2002–2004) in the human lung alveolar epithelial cell line, A549. The spike protein of SARS-CoV-1 is 76–78% identical to that of SARS-CoV-2 [27]. In their study, it was shown that the binding of the full-length spike protein to ACE2 triggered the casein kinase II-dependent activation of activator protein-1 (AP-1) transcription factor and subsequent gene transcriptional events [26]. Their finding on SARS-CoV-1 [26] and ours on SARS-CoV-2 [21] indicate that the spike protein remarkably functionally converts ACE2 (that is normally a peptidase enzyme) into a membrane receptor for cell signaling that uses the spike protein as a ligand for its activation (Figure 2).
Vaccines 09 00036 g002 550

Figure 2. Biological functions of ACE2. In physiological situations, ACE2 functions as a carboxypeptidase enzyme that catalyzes the hydrolysis of angiotensin II (Ang II) into Ang(1–7) by cleaving off a phenylalanine (Phe). In the presence of the spike protein, this enzyme becomes a membrane receptor for cell signaling that uses the spike protein as a ligand for its activation.
Kuba et al. [28] showed that the injection of mice with recombinant SARS-CoV-1 spike protein reduced the ACE2 expression and worsened the acid-induced lung injury. In mice with an acid-induced lung injury, the recombinant SARS-CoV-1 spike protein dramatically increased angiotensin II, and the angiotensin receptor inhibitor losartan attenuated the spike protein-induced enhancement of lung injury [28]. Thus, these in vivo studies demonstrated that the spike protein of SARS-CoV-1 (without the rest of the virus) reduces the ACE2 expression, increases the level of angiotensin II, and exacerbates the lung injury.
The SARS-CoV-2 spike protein without the rest of the viral components has also been shown to activate cell signaling by Patra et al. [29]. The authors reported that the full-length SARS-CoV-2 spike protein expressed by the means of transient transfection, either in the human lung alveolar epithelial cell line A549 or in the human liver epithelial cell line Huh7.5, activated NF-κB and AP-1 transcription factors as well as p38 and ERK mitogen-activated protein kinases, releasing interleukin-6. This cell signaling cascade was found to be triggered by the SARS-CoV-2 spike protein downregulating the ACE2 protein expression, subsequently activating the angiotensin II type 1 receptor [29]. These experiments using transient transfection may reflect the intracellular effects of the spike protein that could be triggered by the RNA- and viral vector-based vaccines.
These results collectively reinforce the idea that human cells are sensitively affected by the extracellular and/or intracellular spike proteins though the activation of cell signal transduction.

4. Pulmonary Hypertension​

PAH is a serious disease without a cure that can affect males and females of any age including children. The increased pulmonary vascular resistance in PAH results in right heart failure and subsequently death. Patients diagnosed with PAH only live for 2–3 years from the time of diagnosis on average if untreated [30,31]. Even with currently available therapies, only 60–70% of PAH patients survive for three years [32,33,34,35]. PAH is hard to detect because its symptoms (e.g., shortness of breath, fatigue, and dizziness) are similar to those of other common non-life threatening conditions, and the official diagnosis for PAH must be made through invasive right heart catheterization [36]. Endothelial dysfunction is a common feature of patients with PAH and COVID-19 [37,38].
PAH “outbreaks” have occurred in association with exposure to certain drugs or toxins [39]. A major outbreak of PAH occurred in 1965 and was associated with aminorex, a weight-loss stimulating drug [39,40]. Approximately 0.2% of people who took this drug developed PAH [40]. An epidemic was observed two years after the introduction of aminorex, and half of the patients died 10 years after the epidemic [39].
We studied pulmonary vessels of COVID-19 patients and those of H1N1 influenza-infected patients who died of ARDS [21]. The pulmonary arteries of postmortem COVID-19 patient lungs consistently exhibited histological characteristics of vascular wall thickening, mainly due to the hypertrophy of the tunica media. Detailed pathological analysis revealed that the boundaries between the vessels and the surrounding lung parenchyma have lost clarity, the SMCs of the middle lining of the arteries have enlarged, the nuclei of SMCs have swollen, and vacuoles have been generated in the cytoplasm of SMCs [21]. A morphometric analysis determined that the median pulmonary vascular wall thickness values were 15.4 μm for the COVID-19 patients and 6.7 μm for the influenza patients, and these values were significantly different from each other [21]. Pulmonary vascular wall thickening in COVID-19 patients was also observed on the computed tomography scan of the chest [41,42]. Thus, these results together indicated that COVID-19 is associated with pulmonary vascular wall thickening. Investigations on whether this pulmonary vascular wall thickening is related to clinically significant PAH and the role of the spike protein in the pathogenesis of PAH are warranted.

5. RBD Only-Containing SARS-CoV-2 Spike Protein Does Not Elicit Cell Signaling in Human Cells​

In contrast to the full-length spike protein [26,29] or the full-length SARS-CoV-2 spike protein S1 subunit [21], we found that the RBD only-containing protein (Figure 1) did not promote cell signaling. Our Western blotting results monitoring the MEK activation showed that the mean ± SEM phosphorylated MEK to MEK protein ratio values were 0.05 ± 0.003 (untreated), 1.9 ± 0.07 (treated with the full-length S1 protein), and 0.05 ± 0.003 (treated with the RBD only-containing protein) for human pulmonary artery SMCs; and 0.09 ± 0.006 (untreated), 0.90 ± 0.06 (treated with the full-length S1 protein), and 0.10 ± 0.003 (treated with the RBD only-containing protein) for human pulmonary artery endothelial cells [21].
The different effects of the full-length S1 and RBD only-containing proteins may be important considering that BNT162b2 and many other COVID-19 vaccines express the full-length spike protein, while the BNT162b1 vaccine encodes only the RBD region [9,10,11,12,13,14,15,16,17,18,19,20]. There are some other RBD-based COVID-19 vaccines being developed as well [43]. It is possible that the RBD-based vaccines are less immunogenic, but may not affect the host cells. Thus, they may be less risky considering potential long-term adverse effects. However, in the in vivo study of the SARS-CoV-1 spike protein described above [28], a deletion mutant that only contained the RBD also worsened the acid-induced lung failure, like the full-length spike protein. Thus, further work is needed to understand effects of the full-length spike protein and the RBD-only containing protein in various biological processes.

6. Discussion​

It is generally thought that the sole function of viral membrane fusion proteins is to allow the viruses to bind to the host cells for the purpose of viral entry into the cells, so that the genetic materials can be released and the viral replication and amplification can take place. However, recent observations suggest that the SARS-CoV-2 spike protein can by itself trigger cell signaling that can lead to various biological processes. It is reasonable to assume that such events, in some cases, result in the pathogenesis of certain diseases.
Our laboratory only tested the effects of the SARS-CoV-2 spike protein in lung vascular cells and those implicated in the development of PAH. However, this protein may also affect the cells of systemic and coronary vasculatures, eliciting other cardiovascular diseases such as coronary artery disease, systemic hypertension, and stroke. In addition to cardiovascular cells, other cells that express ACE2 have the potential to be affected by the SARS-CoV-2 spike protein, which may cause adverse pathological events. Thus, it is important to consider the possibility that the SARS-CoV-2 spike protein produced by the new COVID-19 vaccines triggers cell signaling events that promote PAH, other cardiovascular complications, and/or complications in other tissues/organs in certain individuals (Figure 3). We will need to monitor carefully the long-term consequences of COVID-19 vaccines that introduce the spike protein into the human body. Furthermore, while human data on the possible long-term consequences of spike protein-based COVID-19 vaccines will not be available soon, it is imperative that appropriate experimental animal models are employed as soon as possible to ensure that the SARS-CoV-2 spike protein does not elicit any signs of the pathogenesis of PAH or any other chronic pathological conditions.
Vaccines 09 00036 g003 550

Figure 3. Possible actions of the SARS-CoV-2 spike protein. The SARS-CoV-2 spike protein of the intact virus targets ACE2 of the host cells to facilitate the membrane fusion and the viral entry. The SARS-CoV-2 spike protein also elicits cell signaling in human cells [21,29]. COVID-19 vaccines introduce the spike protein into the human body. In addition to eliciting an immune response that suppresses the viral entry, the spike protein produced by the COVID-19 vaccines may also affect the host cells, possibly triggering adverse events. Further investigations addressing this possibility are warranted.

7. Conclusions​

In conclusion, the recent advancement in the SARS-CoV-2 spike protein-based COVID-19 vaccine development is exciting and has shed light on how to end the current pandemic. These vaccines should benefit elderly people with underlying conditions if they do not exhibit any acute adverse events. However, we need to consider their long-term consequences carefully, especially when they are administered to otherwise healthy individuals as well as young adults and children. In addition to evaluating data that will become available from SARS-CoV-2 infected individuals as well as those who received the spike protein-based vaccines, further investigations of the effects of the SARS-CoV-2 spike protein in human cells and appropriate animal models are warranted.

Excellent, thank you.
 

ddjd

Member
Joined
Jul 13, 2014
Messages
6,677
IT'S NOT LOOKING GOOD FOR THE PFIZER VACCINE.
⬇️
⬇️

FROM THE CDC; 3,150 people vaccinated in ONE DAY are "unable to perform normal daily activities, unable to work" after vaccination.
This is a massive 2.7% of people who can no longer work after having the Pfizer vaccine.
https://www.cdc.gov/.../slides-12-19/05-COVID-CLARK.pdf
Portuguese health worker, 41, dies two days after getting the Pfizer covid vaccine as her father says he 'wants answers'
https://trib.al/eEWi66p
Mexican doctor hospitalized after receiving COVID-19 vaccine
https://www.reuters.com/.../health-coronavirus-mexico...
Hundreds of Israelis get infected with Covid-19 after receiving Pfizer/BioNTech vaccine.
https://www.rt.com/.../511332-israel-vaccination.../
Wife of 'perfectly healthy' Miami doctor, 56, who died of a blood disorder 16 days after getting Pfizer Covid-19 vaccine is certain it was triggered by the jab, as drug giant investigates first death with a suspected link to shot.
https://www.dailymail.co.uk/.../Miami-doctor-58-dies...
75-year-old Israeli man dies 2 hours after getting Covid-19 vaccine.
https://www.israelnationalnews.com/News/News.aspx/293865
Death of Swiss man after Pfizer vaccine.
https://www.reuters.com/.../us-health-coronavirus-swiss...
88-year-old collapses and dies several hours after being vaccinated.
https://www.israelnationalnews.com/News/News.aspx/293952
Thousands negatively affected after getting Covid-19 vaccine.
https://m.theepochtimes.com/thousands-negatively-affected...
Hospital worker with no prior allergies in intensive care with severe reaction after Pfizer Covid vaccine.
https://metro.co.uk/.../hospital-worker-in-intensive.../
4 volunteers develop FACIAL PARALYSIS after taking Pfizer Covid-19 jab, prompting FDA to recommend ‘surveillance for cases’.
https://www.rt.com/.../509081-pfizer-vaccine-fda-bells.../
Investigation launched as 2 people die in Norway nursing home days after receiving Pfizer’s Covid-19 vaccine.
https://www.rt.com/.../511623-norway-covid19-vaccine-deaths/
Hundreds Sent to Emergency Room After Getting COVID-19 Vaccines
https://m.theepochtimes.com/hundreds-sent-to-emergency...
U.S. officials report more severe allergic reactions to COVID-19 vaccines.
https://www.google.com/.../mobi.../article/amp/idUSKBN29B2GS
NHS told not to give Covid vaccine to those with history of allergic reactions.
https://www.google.com/.../pfizer-covid-vaccine-nhs...
COVID-19: Single vaccine dose leads to 'greater risk' from new coronavirus variants, South African experts warn
http://news.sky.com/.../covid-19-single-vaccine-dose...
CDC reveals at least 21 Americans have suffered life threatening allergic reactions to Pfizer's COVID vaccine
http://www.dailymail.co.uk/.../At-21-Americans-life...
Woman experiences side effects of COVID-19 vaccine
http://www.everythinglubbock.com/.../woman.../amp/
COVID Vaccine Side Effects More Common After 2nd Dose.
http://www.boston.cbslocal.com/.../covid-vaccine.../amp/
Bulgaria Reports 4 Cases Of Side Effects From Pfizer Covid Vaccine.
http://www.ndtv.com/.../bulgaria-reports-4-cases-of-side...
Two NHS workers suffer allergic reaction to Pfizer vaccine.
https://www.google.com/.../coronavirus-news-vaccine.../amp/
 

ddjd

Member
Joined
Jul 13, 2014
Messages
6,677
"Let’s make sure we are clear… This is not a vaccine. They are using the term “vaccine” to sneak this thing under public health exemptions. This is not a vaccine.
This is mRNA packaged in a fat envelope that is delivered to a cell. It is a medical device designed to stimulate the human cell into becoming a pathogen creator. It is not a vaccine. Vaccines actually are a legally defined term under public health law; they are a legally defined term under CDC and FDA standards.[1] And the vaccine specifically has to stimulate both the immunity within the person receiving it and it also has to disrupt transmission.
And that is not what this is. They (Moderna and Pfizer) have been abundantly clear in saying that the mRNA strand that is going into the cell is not to stop the transmission, it is a treatment. But if it was discussed as a treatment, it would not get the sympathetic ear of public health authorities because then people would say, “What other treatments are there?
The use of the term vaccine is unconscionable for both the legal definition and also it is actually the sucker punch to open and free discourse… Moderna was started as a chemotherapy company for cancer, not a vaccine manufacturer for SARSCOV2. If we said we are going to give people prophylactic chemotherapy for the cancer they don’t yet have, we’d be laughed out of the room because it’s a stupid idea. That’s exactly what this is. This is a mechanical device in the form of a very small package of technology that is being inserted into the human system to activate the cell to become a pathogen manufacturing site.
And I refuse to stipulate in any conversations that this is in fact a vaccine issue. The only reason why the term is being used is to abuse the 1905 Jacobson case that has been misrepresented since it was written. And if we were honest with this, we would actually call it what it is: it is a chemical pathogen device that is actually meant to unleash a chemical pathogen production action within a cell. It is a medical device, not a drug because it meets the CDRH definition of a device. It is not a living system, it is not a biologic system, it is a physical technology - it happens to just come in the size of a molecular package.
So, we need to be really clear on making sure we don’t fall for their game. Because their game is if we talk about it as a vaccine then we are going to get into a vaccine conversation but this is not, by their own admission, a vaccine. As a result it must be clear to everyone listening that we will not fall for this failed definition just like we will not fall for their industrial chemical definition of health. Both of them are functionally flawed and are an implicit violation of the legal construct that is being exploited. I get frustrated when I hear activists and lawyers say, “we are going to fight the vaccine”. If you stipulate it’s a vaccine you’ve already lost the battle. It’s not a vaccine. It is made to make you sick.
80% of the people exposed to SARSCOV2 are asymptomatic carriers. 80% of people who get this injected into them experience a clinical adverse event. You are getting injected with a chemical substance to induce illness, not to induce an immuno-transmissive response. In other words, nothing about this is going to stop you from transmitting anything. This is about getting you sick and having your own cells be the thing that get you sick.
When the paymaster for the distribution of information happens to be the industry that’s doing the distributing, we lose. Because the only narrative is the one that will be compensated by the people writing the check. That goes for our politicians… and our media - it has been paid for - if you follow the money you realize there is no non-conflicted voice on any network."
- Dr. David Martin, Jan 5th 2021.
 

Mossy

Member
Joined
Jun 2, 2017
Messages
2,043
"Let’s make sure we are clear… This is not a vaccine. They are using the term “vaccine” to sneak this thing under public health exemptions. This is not a vaccine.
This is mRNA packaged in a fat envelope that is delivered to a cell. It is a medical device designed to stimulate the human cell into becoming a pathogen creator. It is not a vaccine. Vaccines actually are a legally defined term under public health law; they are a legally defined term under CDC and FDA standards.[1] And the vaccine specifically has to stimulate both the immunity within the person receiving it and it also has to disrupt transmission.
And that is not what this is. They (Moderna and Pfizer) have been abundantly clear in saying that the mRNA strand that is going into the cell is not to stop the transmission, it is a treatment. But if it was discussed as a treatment, it would not get the sympathetic ear of public health authorities because then people would say, “What other treatments are there?
The use of the term vaccine is unconscionable for both the legal definition and also it is actually the sucker punch to open and free discourse… Moderna was started as a chemotherapy company for cancer, not a vaccine manufacturer for SARSCOV2. If we said we are going to give people prophylactic chemotherapy for the cancer they don’t yet have, we’d be laughed out of the room because it’s a stupid idea. That’s exactly what this is. This is a mechanical device in the form of a very small package of technology that is being inserted into the human system to activate the cell to become a pathogen manufacturing site.
And I refuse to stipulate in any conversations that this is in fact a vaccine issue. The only reason why the term is being used is to abuse the 1905 Jacobson case that has been misrepresented since it was written. And if we were honest with this, we would actually call it what it is: it is a chemical pathogen device that is actually meant to unleash a chemical pathogen production action within a cell. It is a medical device, not a drug because it meets the CDRH definition of a device. It is not a living system, it is not a biologic system, it is a physical technology - it happens to just come in the size of a molecular package.
So, we need to be really clear on making sure we don’t fall for their game. Because their game is if we talk about it as a vaccine then we are going to get into a vaccine conversation but this is not, by their own admission, a vaccine. As a result it must be clear to everyone listening that we will not fall for this failed definition just like we will not fall for their industrial chemical definition of health. Both of them are functionally flawed and are an implicit violation of the legal construct that is being exploited. I get frustrated when I hear activists and lawyers say, “we are going to fight the vaccine”. If you stipulate it’s a vaccine you’ve already lost the battle. It’s not a vaccine. It is made to make you sick.
80% of the people exposed to SARSCOV2 are asymptomatic carriers. 80% of people who get this injected into them experience a clinical adverse event. You are getting injected with a chemical substance to induce illness, not to induce an immuno-transmissive response. In other words, nothing about this is going to stop you from transmitting anything. This is about getting you sick and having your own cells be the thing that get you sick.
When the paymaster for the distribution of information happens to be the industry that’s doing the distributing, we lose. Because the only narrative is the one that will be compensated by the people writing the check. That goes for our politicians… and our media - it has been paid for - if you follow the money you realize there is no non-conflicted voice on any network."
- Dr. David Martin, Jan 5th 2021.
Thanks for sharing. Very informative.
 
B

Blaze

Guest
"Let’s make sure we are clear… This is not a vaccine. They are using the term “vaccine” to sneak this thing under public health exemptions. This is not a vaccine.
This is mRNA packaged in a fat envelope that is delivered to a cell. It is a medical device designed to stimulate the human cell into becoming a pathogen creator. It is not a vaccine. Vaccines actually are a legally defined term under public health law; they are a legally defined term under CDC and FDA standards.[1] And the vaccine specifically has to stimulate both the immunity within the person receiving it and it also has to disrupt transmission.
And that is not what this is. They (Moderna and Pfizer) have been abundantly clear in saying that the mRNA strand that is going into the cell is not to stop the transmission, it is a treatment. But if it was discussed as a treatment, it would not get the sympathetic ear of public health authorities because then people would say, “What other treatments are there?
The use of the term vaccine is unconscionable for both the legal definition and also it is actually the sucker punch to open and free discourse… Moderna was started as a chemotherapy company for cancer, not a vaccine manufacturer for SARSCOV2. If we said we are going to give people prophylactic chemotherapy for the cancer they don’t yet have, we’d be laughed out of the room because it’s a stupid idea. That’s exactly what this is. This is a mechanical device in the form of a very small package of technology that is being inserted into the human system to activate the cell to become a pathogen manufacturing site.
And I refuse to stipulate in any conversations that this is in fact a vaccine issue. The only reason why the term is being used is to abuse the 1905 Jacobson case that has been misrepresented since it was written. And if we were honest with this, we would actually call it what it is: it is a chemical pathogen device that is actually meant to unleash a chemical pathogen production action within a cell. It is a medical device, not a drug because it meets the CDRH definition of a device. It is not a living system, it is not a biologic system, it is a physical technology - it happens to just come in the size of a molecular package.
So, we need to be really clear on making sure we don’t fall for their game. Because their game is if we talk about it as a vaccine then we are going to get into a vaccine conversation but this is not, by their own admission, a vaccine. As a result it must be clear to everyone listening that we will not fall for this failed definition just like we will not fall for their industrial chemical definition of health. Both of them are functionally flawed and are an implicit violation of the legal construct that is being exploited. I get frustrated when I hear activists and lawyers say, “we are going to fight the vaccine”. If you stipulate it’s a vaccine you’ve already lost the battle. It’s not a vaccine. It is made to make you sick.
80% of the people exposed to SARSCOV2 are asymptomatic carriers. 80% of people who get this injected into them experience a clinical adverse event. You are getting injected with a chemical substance to induce illness, not to induce an immuno-transmissive response. In other words, nothing about this is going to stop you from transmitting anything. This is about getting you sick and having your own cells be the thing that get you sick.
When the paymaster for the distribution of information happens to be the industry that’s doing the distributing, we lose. Because the only narrative is the one that will be compensated by the people writing the check. That goes for our politicians… and our media - it has been paid for - if you follow the money you realize there is no non-conflicted voice on any network."
- Dr. David Martin, Jan 5th 2021.
Good post---thank you.
 

Steve

Member
Joined
Nov 9, 2016
Messages
444
I've been listening to a lot of his material.....has a really good way of digging up the facts and explaining them clearly. Although even then I still have to read something 3 or 4 times until it's crystal clear to me. Science is hard. :)
 

J.R.K

Member
Joined
Aug 4, 2020
Messages
1,836
I am kind of new here, but I have been trying to get up to speed to be able to converse somewhat intelligently on any of the material discussed in the forum.
While I have not been an,”anti vaxxer” in the past, as I learn more about the point of view to try to gain an understanding of this group I have to admit that the points of opposition with a science to validate their points I must admit my viewpoint on the topic has shifted.
That being said though even if I was a ,”pro vaxxer” as it were, I still would question the speed at which this ,”new vaccine” was produced and brought into widespread distribution with a minimal amount clinical trial testing.
The fact that the manufacturers (Pfizer Bio N Tech and Moderna) both have legal immunity for any and all unexpected reactions to these products.
Not to mention the unknown long term side effects to not only the newly vaccinated, but possibly their future generations.
As well as the growing list of people worldwide that are reacting negatively to “the jab”should give even the most staunch to reconsider clambering to get to the front of the line to roll up their sleeve.
 

Fred

Member
Joined
Jul 25, 2013
Messages
487
I am kind of new here, but I have been trying to get up to speed to be able to converse somewhat intelligently on any of the material discussed in the forum.
While I have not been an,”anti vaxxer” in the past, as I learn more about the point of view to try to gain an understanding of this group I have to admit that the points of opposition with a science to validate their points I must admit my viewpoint on the topic has shifted.
That being said though even if I was a ,”pro vaxxer” as it were, I still would question the speed at which this ,”new vaccine” was produced and brought into widespread distribution with a minimal amount clinical trial testing.
The fact that the manufacturers (Pfizer Bio N Tech and Moderna) both have legal immunity for any and all unexpected reactions to these products.
Not to mention the unknown long term side effects to not only the newly vaccinated, but possibly their future generations.
As well as the growing list of people worldwide that are reacting negatively to “the jab”should give even the most staunch to reconsider clambering to get to the front of the line to roll up their sleeve.
Keep in mind that this is NOT a traditional vaccine which uses a killed/attenuated virus. The mRNA vaccine is a whole different animal, so none of the historical arguments about vaccine safety/efficacy apply, despite constant MSM claims to the contrary. Also note that the online dictionaries have recently changed the definition of "vaccine", (intentionally) adding to the confusion.
 

J.R.K

Member
Joined
Aug 4, 2020
Messages
1,836
Keep in mind that this is NOT a traditional vaccine which uses a killed/attenuated virus. The mRNA vaccine is a whole different animal, so none of the historical arguments about vaccine safety/efficacy apply, despite constant MSM claims to the contrary. Also note that the online dictionaries have recently changed the definition of "vaccine", (intentionally) adding to the confusion.
All extremely valid points Fred!
The baffling part to me is why in the presence of all these unanswered questions is there such an incredible amount of herd mentality to just line up and take this new vaccine, without any reservation or concern about long term side effects not only in their own lives but quite possibly as Dr Peat intuitively points out, unknown side effects that may only arise in two to three generations.
 

Perry Staltic

Member
Joined
Dec 14, 2020
Messages
8,186
Research indicating SARSCov2 spike proteins may induce physiological responses via cellular signaling (in addition to facilitating intracellular viral replication), implying possible pathological consequences of mRNA gene therapies that transfect humans with spike proteins. This might explain why young, healthy people have dropped dead of heart attacks after receiving a mRNA gene therapy "vaccine".

It was found that the treatment of cultured primary human pulmonary artery smooth muscle cells (SMCs) or human pulmonary artery endothelial cells with the recombinant SARS-CoV-2 spike protein S1 subunit is sufficient to promote cell signaling without the rest of the viral components [21]. Furthermore, our analysis of the postmortem lung tissues of patients who died of COVID-19 has determined that these patients exhibited pulmonary vascular wall thickening, a hallmark of pulmonary arterial hypertension (PAH) [21]. Based on these results, we proposed that the SARS-CoV-2 spike protein (without the rest of the viral components) triggers cell signaling events that may promote pulmonary vascular remodeling and PAH [pulmonary arterial hypertension] as well as possibly other cardiovascular complications

 
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Perry Staltic

Member
Joined
Dec 14, 2020
Messages
8,186
Intriguing. It was known 10 years ago that ACE2 acted as a receptor to the SARSCov1 spike protein for cell signal transduction. (link above)

While ACE2 is now well known as a ‘receptor’ to which the SARS-CoV-2 spike protein binds on human host cells in order to facilitate the membrane fusion and gain viral entry, the usual physiological function of ACE2 is not to serve as a membrane receptor to transduce intracellular signals. ACE2 is a type I integral membrane protein that functions as a carboxypeptidase, cleaving angiotensin II to angiotensin (1–7) and regulating blood pressure [24,25] (Figure 2). However, ten years ago, Chen et al. [26] reported the intriguing findings showing that ACE2 acts as a membrane receptor for cell signal transduction in response to the spike protein of SARS-CoV (now also known as SARS-CoV-1, the virus that caused the SARS outbreak in 2002–2004) in the human lung alveolar epithelial cell line, A549. The spike protein of SARS-CoV-1 is 76–78% identical to that of SARS-CoV-2 [27]. In their study, it was shown that the binding of the full-length spike protein to ACE2 triggered the casein kinase II-dependent activation of activator protein-1 (AP-1) transcription factor and subsequent gene transcriptional events [26]. Their finding on SARS-CoV-1 [26] and ours on SARS-CoV-2 [21] indicate that the spike protein remarkably functionally converts ACE2 (that is normally a peptidase enzyme) into a membrane receptor for cell signaling that uses the spike protein as a ligand for its activation (Figure 2).
 
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Perry Staltic

Member
Joined
Dec 14, 2020
Messages
8,186
Wow. Reduction of ACE2 expression via SARSCov2 binding is considered to destabilize the renin angiotensin system and shift it towards it's inflammatory/vasoconstrictive/prothrombotic axis. This shows the SARSCov1 spike protein itself, without the virus, could do that.

Kuba et al. [28] showed that the injection of mice with recombinant SARS-CoV-1 spike protein reduced the ACE2 expression and worsened the acid-induced lung injury. In mice with an acid-induced lung injury, the recombinant SARS-CoV-1 spike protein dramatically increased angiotensin II, and the angiotensin receptor inhibitor losartan attenuated the spike protein-induced enhancement of lung injury [28]. Thus, these in vivo studies demonstrated that the spike protein of SARS-CoV-1 (without the rest of the virus) reduces the ACE2 expression, increases the level of angiotensin II, and exacerbates the lung injury.
 
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J.R.K

Member
Joined
Aug 4, 2020
Messages
1,836
Thank you for the insight Perry Staltic. While I am nowhere near up to speed in understanding all the scientific lingo in the coding for various lab and physiological descriptions. I do get the gist of the message.
One other wild card factor that has yet to be determined is the affect that the unrolling of 5G will have upon these mRNA vaccines, as well as how it will affect both the signal sent and messages received by the cellular matrix.
There is to many unanswered questions and the myriad of outcomes based upon both known factors, unknown factors, as well as the infinite combinations that could be, within each given person.
For me I think that I will stick with chamomile teas, some collagen, vitamin A,D,E,K and some Aspirin. Leaving the current ,”animal trials”, to the more brave souls out there. But the adage ,”fools rush in where angels fear to tread”, seems to be more fitting IMO.
 

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