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Be aware of SARS-CoV-2 spike protein: There is more than meets the eye
Abstract
Human The COVID-19 pandemic necessitated the rapid production of vaccines aimed at the production of neutralizing antibodies against the COVID-19 spike protein required for the corona virus binding to target cells. The best well-known vaccines have utilized either mRNA or an adenovirus vector to direct human cells to produce the spike protein against which the body produces mostly neutralizing antibodies. However, recent reports have raised some skepticism as to the biologic actions of the spike protein and the types of antibodies produced. One paper reported that certain antibodies in the blood of infected patients appear to change the shape of the spike protein so as to make it more likely to bind to cells, while other papers showed that the spike protein by itself (without being part of the corona virus) can damage endothelial cells and disrupt the blood-brain barrier. These findings may be even more relevant to the pathogenesis of long-COVID syndrome that may affect as many as 50% of those infected with SARS-CoV-2. In COVID-19, a response to oxidative stress is required by increasing anti-oxidant enzymes. In this regard, it is known that polyphenols are natural anti-oxidants with multiple health effects. Hence, there are even more reasons to intervene with the use of anti-oxidant compounds, such as luteolin, in addition to available vaccines and anti-inflammatory drugs to prevent the harmful actions of the spike protein.
... The mRNA vaccines are typically administered through the intramuscular route. After being injected into the muscle (usually the deltoid muscle), the vaccine is taken up by immune cells and transported through the lymphatic system to the lymph nodes, where it can stimulate an immune response [14]. However, it is possible for the vaccine to be inadvertently injected into a blood vessel. ...
... Studies have estimated that this may happen in about 1 in 800 injections, although the actual rate may vary depending on the technique used for injection. The phenomenon may result in the vaccine being delivered directly to the cardiac muscle, which may be responsible for the increased incidence of myocarditis which has been observed following COVID-19 mRNA vaccination [14]. A recent report by the Australian Health Authority demonstrated that the mRNA vaccine lipid nanoparticles are distributed throughout the body, including concentrations in the lymph nodes, spleen and bone marrow, and this report also found that the spike protein was present in the blood for up to 14 days following mRNA vaccination (T. ...
... A recent report by the Australian Health Authority demonstrated that the mRNA vaccine lipid nanoparticles are distributed throughout the body, including concentrations in the lymph nodes, spleen and bone marrow, and this report also found that the spike protein was present in the blood for up to 14 days following mRNA vaccination (T. It has been reported that certain antibodies in the blood of COVID-19 infected patients appear to change the shape of the spike protein to make it more likely to bind to cells, while other studies showed that the spike protein by itself (without being part of the corona virus) can damage endothelial cells and disrupt the blood-brain barrier [14]. These findings may be even more relevant to the pathogenesis of long-COVID syndrome that may affect as many as 50% of those infected with SARS-CoV-2. ...
... mRNA and viral vector vaccines involve the bodily synthesis of the SARS-CoV-2 2 Spike protein as the foundation of the immune response, while protein subunit vaccines utilize injection of exogenous Spike protein, bypassing the need for genetic mechanisms 3 . Regardless of the vaccine platform used, circulating SARS-CoV-2 Spike protein is the likely detrimental agent through which COVID-19 vaccines cause biological harm [4][5][6][7][8][9][10][11][12][13] . Spike protein can initiate the breakdown and internalization of ACE2 receptors, which may disrupt the renin-angiotensin system (RAS) and lead to increased inflammation, vasoconstriction, and thrombosis 4. Further, Spike protein can stimulate platelets and inflict damage to the endothelium, which can lead to arterial and venous thrombosis 5 . ...
... Moreover, a recent study found that repeated COVID-19 vaccination with mRNA-based vaccines leads to the production of abnormally high concentrations of IgG4 antibodies 7 . These antibodies can fail to neutralize Spike protein, which has been shown to circulate for at least 28 days, cause immune suppression, and promote the development of autoimmune diseases including myocarditis [7][8][9][10][11][12][13] . ...
... We established that all 28 deaths are causally linked to COVID-19 vaccination by independent review of the clinical information presented in each paper. Our data are consistent with the overall epidemiological literature (PUBMED search for [COVID-19 vaccination] * [myocarditis] = 994 papers) 9 concerning COVID-19 vaccine-induced myocarditis where the Bradford Hill Criteria 39 support causality from an epidemiological perspective. This includes biological plausibility, temporal association, internal and external validity, coherence, analogy, and reproducibility with each successive report of myocarditis-related death after COVID-19 vaccination. ...
Background: COVID-19 vaccines have been linked to myocarditis which in some circumstances can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. Methods: We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-related myocarditis through July 3rd, 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included, without imposing any additional restrictions. Causality in each case was determined by three independent reviewers with cardiac pathology experience and expertise. Results: We initially identified 1,691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In 2 cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome (MIS). The mean and median number of days from last COVID-19 vaccination until death was 6.2 and 3 days, respectively. Most of the deaths occurred within a week from the last injection. We established that all 28 deaths were causally linked to COVID-19 vaccination by independent adjudication. Conclusions: The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death from suspected myocarditis in cases where sudden, unexpected death has occurred in a vaccinated person. Urgent investigation is required for the purpose of risk stratification and mitigation in order to reduce the population occurrence of fatal COVID-19 vaccine-induced myocarditis.
... The extent of subclinical danger, as well as the increase in sudden and unexplained deaths motivates the diagnosis of vaccine injury through biomarkers. One immediate biomarker that comes to the fore is testing for the presence of the spike protein or its subunits in plasma [3], as it is a major pathological agent driving vaccine injury, long covid, as well as acute covid-19 infection [4]. ...
... These include troponin, D-dimer and C-reactive protein [3]. [4]. These biomarkers are specific to cardiac injury, and will not be able to determine disease aetiology. ...
... The main differentiator between the group with myocarditis and those without was the persistence of full length spike protein, unbound by antibodies [3]. Given that this is the sole gene encoded by most of the vaccines and has multiple documented pathological mechanisms [4], it is a likely aetiological factor in post-vaccination syndrome. ...
Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.
... 3 Regardless of the vaccine platform used, circulating SARS-CoV-2 Spike protein is the likely detrimental agent through which COVID-19 vaccines cause biological harm. [4][5][6][7][8][9][10][11][12][13] Spike protein can initiate the breakdown and internalization of angiotensin-converting enzyme 2 (ACE2) receptors, which may disrupt the reninangiotensin system (RAS) and lead to increased inflammation, vasoconstriction, and thrombosis. 4 Further, Spike protein can stimulate platelets and inflict damage to the endothelium, which can lead to arterial and venous thrombosis. ...
... 7 These antibodies can fail to neutralize Spike protein, which has been shown to circulate for at least 28 days, cause immune suppression, and promote the development of autoimmune diseases including myocarditis. [7][8][9][10][11][12][13] In June 2021, the US Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) issued a joint warning on myocarditis occurring after mRNA COVID-19 vaccination. 14 A PubMed search performed at the time of writing for 'myocarditis' and 'COVID-19 vaccination' yielded 994 results, indicating extensive interest in COVID-19 vaccine-induced myocarditis among researchers. ...
COVID‐19 vaccines have been linked to myocarditis, which, in some circumstances, can be fatal. This systematic review aims to investigate potential causal links between COVID‐19 vaccines and death from myocarditis using post‐mortem analysis. We performed a systematic review of all published autopsy reports involving COVID‐19 vaccination‐induced myocarditis through 3 July 2023. All autopsy studies that include COVID‐19 vaccine‐induced myocarditis as a possible cause of death were included. Causality in each case was assessed by three independent physicians with cardiac pathology experience and expertise. We initially identified 1691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In two cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome. The mean age of death was 44.4 years old. The mean and median number of days from last COVID‐19 vaccination until death were 6.2 and 3 days, respectively. We established that all 28 deaths were most likely causally linked to COVID‐19 vaccination by independent review of the clinical information presented in each paper. The temporal relationship, internal and external consistency seen among cases in this review with known COVID‐19 vaccine‐induced myocarditis, its pathobiological mechanisms, and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests that there is a high likelihood of a causal link between COVID‐19 vaccines and death from myocarditis.
... SARS-CoV-2 is a single-stranded RNA (ssRNA) virus with four essential proteins: 1) the spike (S) protein that enables its attachment and entrance into host cells, 2) the membrane (M) protein that forms the viral membrane, 3) the nucleocapsid (N) protein which supports the formation of nucleocapsid by binding to viral RNA and assists in virus budding, RNA replication, and mRNA replication, and 4) the envelope (E) protein which is involved in viral assembly, release, and pathogenesis (Chung et al., 2021). Detrimental effects of S protein include SARS-CoV-2 entry into target cells, endothelial damage, pro-inflammatory cytokine release, toll-like receptors (TLRs) activation, microglia stimulation, and molecular mimicry with chaperon and heat shock proteins (HSPs) (Theoharides and Conti, 2021). Type II transmembrane protease serine subfamily (TMPRSS2) plays a vital role in the activation of the SARS-CoV-2 S protein and its binding to angiotensin-converting enzyme 2 (ACE2) (Al-Kuraishy et al., 2021). ...
... TLR7 and TLR8 recognize ssRNA, while TLR2 intercedes the recognition of the S protein (Patil et al., 2020). Virus engagement with ACE2 leads to viral replication in the nucleus, activation of TLR7/8 in the endosomes, and production of pro-inflammatory cytokines (Theoharides and Conti, 2021). After virus entry, the innate recognition of the virus occurs via the activation of anti-viral processes, the recruitment of innate immune cells, and the triggering of the adaptive immune response. ...
Menstrual disturbances are occurred following COVID-19 vaccination.
... SARS-CoV-2 is a single-stranded RNA (ssRNA) virus with four essential proteins: 1) the spike (S) protein that enables its attachment and entrance into host cells, 2) the membrane (M) protein that forms the viral membrane, 3) the nucleocapsid (N) protein which supports the formation of nucleocapsid by binding to viral RNA and assists in virus budding, RNA replication, and mRNA replication, and 4) the envelope (E) protein which is involved in viral assembly, release, and pathogenesis (Chung et al., 2021). Detrimental effects of S protein include SARS-CoV-2 entry into target cells, endothelial damage, pro-inflammatory cytokine release, toll-like receptors (TLRs) activation, microglia stimulation, and molecular mimicry with chaperon and heat shock proteins (HSPs) (Theoharides and Conti, 2021). Type II transmembrane protease serine subfamily (TMPRSS2) plays a vital role in the activation of the SARS-CoV-2 S protein and its binding to angiotensin-converting enzyme 2 (ACE2) (Al-Kuraishy et al., 2021). ...
... TLR7 and TLR8 recognize ssRNA, while TLR2 intercedes the recognition of the S protein (Patil et al., 2020). Virus engagement with ACE2 leads to viral replication in the nucleus, activation of TLR7/8 in the endosomes, and production of pro-inflammatory cytokines (Theoharides and Conti, 2021). After virus entry, the innate recognition of the virus occurs via the activation of anti-viral processes, the recruitment of innate immune cells, and the triggering of the adaptive immune response. ...
Menstruation is a monthly shedding of the uterine wall, presented by menstrual bleeding in women of reproductive age. Menstruation is regulated by fluctuation of estrogen and progesterone, as well as other endocrine and immune pathways. Many women experienced menstrual disturbances after vaccination against the novel coronavirus in the last two years. Vaccine-induced menstrual disturbances have led to discomfort and concern among reproductive-age women, such that some decided not to receive the subsequent doses of the vaccine. Although many vaccinated women report these menstrual disturbances, the mechanism is still poorly understood. This review article discusses the endocrine and immune changes following COVID-19 vaccination and the possible mechanisms of vaccine-related menstrual disturbances.
... As a result of the spike protein's critical role in viral entry, the vaccines that are currently being administered rely on the spike protein as an immunogen [5]. For example, the two main vaccine types for the SARS-CoV-2 virus are the mRNA-based vaccines and the non-replicating viral vector vaccines, both of which provide genetic information that instructs the body's cells to express the spike protein [6]. Once the spike protein is synthesized, neutralizing antibodies are produced and memory cells are stored for protection from a future SARS-CoV-2 infection [2,6]. ...
... For example, the two main vaccine types for the SARS-CoV-2 virus are the mRNA-based vaccines and the non-replicating viral vector vaccines, both of which provide genetic information that instructs the body's cells to express the spike protein [6]. Once the spike protein is synthesized, neutralizing antibodies are produced and memory cells are stored for protection from a future SARS-CoV-2 infection [2,6]. ...
Recombinant SARS-CoV-2 trimeric spike protein produced by mammalian cell culture is a potential candidate for a COVID-19 vaccine. However, this protein is much larger than most typical biopharmaceutical proteins and its large-scale manufacture is therefore challenging. Particularly, its purification using resin-based chromatography is difficult as the diffusive transport of this protein to and from its binding site within the pores of the stationary phase particles is slow. Therefore, very low flow rates need to be used during binding and elution, and this slows down the purification process. Also, due to its large size, the binding capacity of this protein on resin-based media is low. Membrane chromatography is an efficient and scalable technique for purifying biopharmaceuticals. The predominant mode of solute transport in a membrane is convective and hence it is considered better than resin-based chromatography for purifying large proteins. In this paper, we propose a membrane chromatography-based purification method for fast and scalable manufacture of recombinant SARS-CoV-2 trimeric spike protein. A combination of cation exchange z2 laterally-fed membrane chromatography and size exclusion chromatography was found to be suitable for obtaining a homogeneous spike protein sample from mammalian cell culture supernatant. The proposed method is both fast and scalable and could be explored as a method for manufacturing vaccine grade spike protein.
... Finally some papers showed that the spike protein by itself (without being part of the corona virus) can damage endothelial cells and disrupt the blood-brain barrier (92). Nutraceuticals with anti-oxidant and anti-viral properties, such as liposomal blend of the natural flavonoids luteolin and quercetin, could prevent the detrimental actions of spike protein, but further case-control studies in pediatric setting are needed (92)(93)(94). ...
... Finally some papers showed that the spike protein by itself (without being part of the corona virus) can damage endothelial cells and disrupt the blood-brain barrier (92). Nutraceuticals with anti-oxidant and anti-viral properties, such as liposomal blend of the natural flavonoids luteolin and quercetin, could prevent the detrimental actions of spike protein, but further case-control studies in pediatric setting are needed (92)(93)(94). ...
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has milder presentation in children than in adults, mostly requiring only supportive therapy. The immunopathogenic course of COVID-19 can be divided in two distinct but overlapping phases: the first triggered by the virus itself and the second one by the host immune response (cytokine storm). Respiratory failure or systemic involvement as Multisystem Inflammatory Syndrome in Children (MIS-C) requiring intensive care are described only in a small portion of infected children. Less severe lung injury in children could be explained by qualitative and quantitative differences in age-related immune response. Evidence on the best therapeutic approach for COVID-19 lung disease in children is lacking. Currently, the approach is mainly conservative and based on supportive therapy. However, in hospitalized children with critical illness and worsening lung function, antiviral therapy with remdesivir and immunomodulant treatment could be considered the “therapeutic pillars.”
... In this perspective, immunomodulation and targeting key drivers of COVID-19-induced cytokine storm thus became a promising therapeutic approach. That being said, emerging evidence on the unintended effects of immunomodulators, such as vaccine-induced neutralizing antibodies as well as the long-term effect of the virus' own spike protein (long-COVID syndrome) highlight the importance of a multifaceted approach against the COVID-19 pandemic [15]. The arsenal against COVID-19ʹs deadly cytokine storm should therefore be supplemented both with the modulation of disease outcomes, such as the oxidative stress produced by COVID-19, as well as prophylaxis (vaccination and the reduction of viral shedding) [15,16]. ...
... That being said, emerging evidence on the unintended effects of immunomodulators, such as vaccine-induced neutralizing antibodies as well as the long-term effect of the virus' own spike protein (long-COVID syndrome) highlight the importance of a multifaceted approach against the COVID-19 pandemic [15]. The arsenal against COVID-19ʹs deadly cytokine storm should therefore be supplemented both with the modulation of disease outcomes, such as the oxidative stress produced by COVID-19, as well as prophylaxis (vaccination and the reduction of viral shedding) [15,16]. Both of these approaches are outside of the scope of this review, which will focus on the use of immunomodulators for the management of COVID-19. ...
The emergency state caused by COVID-19 saw the use of immunomodulators despite the absence of robust research. To date, the results of relatively few randomized controlled trials have been published, and methodological approaches are riddled with bias and heterogeneity. Anti-SARS-CoV-2 antibodies, convalescent plasma and the JAK inhibitor baricitinib have gained Emergency Use Authorizations and tentative recommendations for their use in clinical practice alone or in combination with other therapies. Anti-SARS-CoV-2 antibodies are predominating the management of non-hospitalized patients, while the inpatient setting is seeing the use of convalescent plasma, baricitinib, tofacitinib, tocilizumab, sarilumab, and corticosteroids, as applicable. Available clinical data also suggest the potential clinical benefit of the early administration of blood-derived products (e.g. convalescent plasma, non-SARS-CoV-2-specific immunoglobins) and the blockade of factors implicated in the hyperinflammatory state of severe COVID-19 (Interleukin 1 and 6; Janus Kinase). Immune therapies seem to have a protective effect and using immunomodulators alone or in combination with viral replication inhibitors and other treatment modalities might prevent progression into severe COVID-19 disease, cytokine storm and death. Future trials should address existing gaps and reshape the landscape of COVID-19 management.
... 80 Recently, as many as 50% of COVID-19 patients, regardless of their disease severity, have been reported to exhibit long-COVID syndrome even months after SARS-CoV-2 viral infection, presenting symptoms such as malaise, fatigue, joint pain, brain fog, chest tightness, shortness of breath, which are very similar to the symptoms observed in Mast Cell Activation Syndrome (MCAS) patients. 46,[91][92][93] Pulmonary fibrosis might result in pulmonary dysfunction, accounting for the chest pain and shortness of breath in long-COVID patients 92 and pulmonary fibrosis has also been reported in SARS survivors post recovery and might represent one of the main complications in COVID-19 patients. 43 Indeed, Tan et al. have reported sustained MC activation at late time point postinfection even when patients were no longer tested positive for SARS-CoV-2 by polymerase chain reaction (PCR), suggesting ongoing, unresolved inflammation in the tissues and thereby long-term tissue damage after infection clearance. ...
... 48 Indeed, luteolin is a much more potent inhibitor for histamine release from MCs comparing to sodium cromoglycate 46 and luteolin can also suppress neuroinflammation and brain fog. 57,91,93 Further, luteolin exhibits broad anti-viral properties as it can bind to the spike protein of SARS-CoV-2 to prevent the virus from entering into the host cells 57,93,97 and can also inhibit SARS-CoV 3CL protease which is required for viral infectivity 97 and therefore luteolin and tetramethoxyluteolin, which are generally considered to be safe, are recommended as dietary supplement for COVID-19 patients 45,46,57,97 ; Avapritinib, Midostaurin and Imatinib which are used in systemic mastocytosis might reduce the number of MCs to prevent hyperinflammation and lung fibrosis in COVID-19 patients 109 ; Rupatadine, which is a dual H1 receptor and PAF antagonist being used to treat rhinitis and chronic spontaneous urticaria patients, might also be applied to inhibit the effects of histamine and PAF released by MCs as well as the activation of MCs by PAF in SARS-CoV-2-infected individuals to suppress their bronchoconstriction, microthrombosis and inflammation 97 ; Anti-inflammatory cytokines, such as IL-37 that inhibit IL-1 are also recommended for dampening the "cytokine storm". 44 Canakinumab can be used as a therapy for cryopyrin-associated periodic syndromes to block IL-1β 22 ; Infliximab, adalimumab, certolizumab pegol, golimumab and etanercept can be applied to neutralize TNF-α for RA patients 109 ; Similarly, tocilizumab and sarilumab against IL-6 receptors are used for treating RA. 109 Therefore, applying these biologics to block proinflammatory cytokines released by MCs or the receptors for these cytokines might help to control the hyperinflammation in COVID-19 patients. ...
Mast cells (MCs) are innate immune cells that widely distribute throughout all tissues and express a variety of cell surface receptors. Upon activation, MCs can rapidly release a diverse array of pre‐formed mediators residing within their secretory granules and newly synthesize a broad spectrum of inflammatory and immunomodulatory mediators. These unique features of MCs enable them to act as sentinels in response to rapid changes within their microenvironment. There is increasing evidence now that MCs play prominent roles in other pathophysiological processes besides allergic inflammation. In this review, we highlight the recent findings on the emerging roles of MCs in the pathogenesis of coronavirus disease‐2019 (COVID‐19) and discuss the potential of MCs as novel therapeutic targets for COVID‐19 and other non‐allergic inflammatory diseases.
... Años sin datos (S/D). (Theoharides, 2021;Bozkurt, 2021;Trougakos et al. 2022;Seneff et al. 2022;Theoharides, 2022;Yonker et al. 2023;Hulscher et al. 2023 (Liu et al. 2021). Se puede esperar que esto interfiera con los efectos protectores del cáncer de BRCA1. ...
The objective of this study was to evaluate the trend that breast
cancer has shown in Baja California Sur from the first year of
registration in 1990 until the impact of COVID-19 vaccination in
2021. The total number of cases in the state and the incidence
rate were analyzed in the general population, by age groups and
gender. The cases in the general population during this period
were 1,161 cases. The most affected gender was female. The most
affected age group was 50-59 years. Of the thirty-one years of
registration, the year with the highest number of reported cases
was 2021 with 124 cases. The incidence rate of new cases during
this second year of confinement and beginning of the COVID-19
vaccination shot up to 18.21, 2 1/2 times higher than in 2020.
... This happened even after the virus was no longer linked to the protein [8,9]. Furthermore, nearly all mRNA-based vaccines now use the spike protein as the primary immunogen, and side effects from spike protein-based vaccine complications are beginning to pile up in the literature [129][130][131][132]. More evidence is needed to understand the cause of vaccine-induced immune thrombotic thrombocytopenia (VITT), with some researchers pointing to the spike protein as a significant contributor, while others disagree. ...
Tackling COVID-19 requires halting virus proliferation and reducing viral complications in humans. Papaya leaf extract (PLE) is well known for its ability to inhibit numerous viral replications in vitro and in vivo and reduce viral complications in humans such as thrombocytopenia and cytokine storm. The goal of this research is to evaluate the possible use of papaya leaf extract as a multifaceted antiviral and potential therapy for COVID-19 using an in-silico docking followed by a 100 ns molecular dynamics simulation (MDS) approach. The targeted proteins are the SARS-CoV-2's proteins such as the nucleocapsid, main protease (MPro), RNA-dependent RNA polymerase (RdRP), spike protein (Wuhan, Delta, and Omicron variants) and human TNF-alpha and alpha-thrombin protein targets. Several compounds from PLE such as protodioscin, clitorin, glycyrrhizic acid, manghaslin, kaempferol–3–(2g–glucosylrutinoside), rutin, isoquercetrin and acacic acid were found to exhibit strong binding to these targets. The free energies of binding (Autodock) with protodioscin, the best PLE compound for nucleocapsid, main protease (MPro), RdRP and spike protein were –13.83, –13.19, –11.62 and –10.77 (Omicron), kcal/mol, respectively, while the TNF-alpha and alpha-thrombin binding free energies were –13.64 and –13.50 kcal/mol, respectively. The calculated inhibition constants for protodioscin were in the nanomolar and picomolar range at 216.34, 27.07, 73.28, and 99.93 pM, respectively, whilst RdRp and spike protein (Omicron) were in the nanomolar range at 3.02 and 12.84 nM, respectively. Protodioscin interacted with key residues of all protein targets. The binding affinity poses were confirmed by molecular dynamics simulation. Analysis of the binding affinities calculated employing the molecular mechanics-Poisson–Boltzmann surface area (MM-PBSA) shows favorable interaction between protodioscin, and all targets based on total binding-free energies corroborating the Autodock's docking results. In conclusion, compounds from PLE, especially protodioscin have good potentials in combating COVID-19.
... We analyzed the molecular pathways of new mRNA vaccines and found they may potentially provoke electric disturbances, specifically regarding their effects on the ACE system and the role of the spike protein in the contest of cardiovascular complication [87,88]. In addition, these observations raise concerns regarding the central role of the ACE system on heart conduction homeostasis and possible detrimental impact of iatrogenic interference with this system in this context. ...
SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk–benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.
... The spike protein -whether from Covid or from vaccine -could represent the key for understand the molecular pathway of the heart conduction abnormality. Binding with high affinity to ACE2, could potentially result in ACE imbalance promoting cardiac complication (87,88). Heart rhythm conduction is highly affected by ACEs and its alteration may promote heart rhythm disorders. ...
-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.
... In view of the possibility that mRNA vaccines may be associated with adverse all-cause mortality a review of potential adverse effects from mRNA vaccination raised several issues which could impact long-, medium-and short-term all-cause mortality [164]. Other studies have raised concerns around neurological side-effects, reverse transcription, and toxicity of the naked spike protein [153,[165][166][167][168][169][170][171]. ...
All vaccines exhibit both specific and non-specific effects. The specific effects are measured by the efficacy against the target pathogen, while the non-specific effects can be detected by the change in all-cause mortality. All-cause mortality data (gender, age band, vaccination history, month of death) between January 2021 and May 2022 was compiled by the Office for National Statistics. COVID-19 vaccination gave good protection on many occasions but less so for younger ages. Each gender and age group shows its own unique vaccination benefit/disbenefit time profile. Individuals are free to make vaccination decisions. For example, women aged 18-39 show a cohort who do not progress beyond the first or second dose. The all-cause mortality outcomes for the Omicron variant showed a very poor response to vaccination with 70% of sex/age/vaccination stage/month combinations increasing all-cause mortality, probably due to unfavorable antigenic distance between the first-generation vaccines and this variant, and additional non-specific effects. The all-cause mortality outcomes of COVID-19 vaccination is far more nuanced than have been widely appreciated, and virus vector appear better than the mRNA vaccines in this specific respect. The latter are seemingly more likely to increase all-cause mortality especially in younger age groups. An extensive discussion/literature review is included to provide potential explanations for the observed unexpected vaccine effects. Full text and Supplementary material at: https://www.preprints.org/manuscript/202304.0248/v1
Note that we are about to submit a version of this paper looking at the effects on non-COVID-19 all-cause mortality (NCACM).After that we aim to return to the all-cause mortality paper.
... The spike protein had been suspected to have more ef fects than its common signature. It was reported by a pa per that the spike protein could change its shape to make it prone to bind to more cells, and some other papers show that it can harm endothelial cells by itself and can disturb the bloodbrain barrier (Theoharides and Conti 2021). Due to the spike protein having a major role in the SARSCoV 2 disease, for the Alpha and Beta Indonesian variants, the mutations in the S gene will be focused on to be analyzed. ...
The SARS‐CoV‐2 virus has been the cause of the global pandemic since the end of 2019. Since then, the virus has mutated to create different types of variants with numerous effects on those infected. This has complicated human intervention for prevention. Indonesia was heavily affected by the pandemic, specifically from May to August 2021, and as a country has recorded many distinct isolates. Thus, characterization of the virus strains from Indonesia is important. GISAID, NCBI BLAST, and MAFFT version 7 were used. There were 9,488 isolates in Indonesia as of November 2021, with the majority including the Delta variant. While most of the isolates have mutations common to those from other countries, there are some atypical ones, such as mutation V1264L in the Delta variant that was suspected to play a role in worsening the pandemic. The Delta variant had the most mutations in the spike protein when compared to the Alpha and Beta variants, giving it important roles in infectivity and vigorous entry into cells, with some general clinical manifestations like fever and sore throat; however, the severity of the Delta variant is attributable to its rapid growth. This is why, from May to November 2021 in Indonesia, cases of the Delta variant rocketed, unlike the other variants.
... The S protein has three structural domains, among which the S1 domain is the most important S protein surface antigen [4]. Due to the difficulty of producing large recombinant proteins (the extracellular domain of the protein S is about 1300 amino acids) and the risk of antibody-dependent enhancement (ADE) of infection, S1 (about 700 amino acids) and its receptor-binding domain (RBD, about 200 amino acids) are widely regarded as the most attractive potential targets for a coronavirus vaccine [7,8]. Human adenovirus serotype 5(HAdV-C5) is widely used in basic virology as a gene therapy and vaccine delivery vector [9]. ...
The development of an efficient and safe coronavirus disease 2019 (COVID-19) vaccine is a crucial approach for managing the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) pandemic in light of current conditions. In this study, we produced a shortened segment of the optimized SARS-CoV-2 spike gene (2043 bp, termed S1) that was able to encode a truncated S1 protein. The protein was tested to determine if it could elicit efficient immunization in mice against SARS-CoV-2. The presence of the S1 protein was confirmed with immunofluorescence and Western blotting. An adenovirus vaccine bearing the S1 gene fragment (Ad-S1) was administered intramuscularly to mice four times over 4 weeks. SARS-CoV-2 S1 protein humoral immunity was demonstrated in all immunized mice. The serum from immunized mice demonstrated excellent anti-infection activity in vitro. A robust humoral immune response against SARS-CoV-2 was observed in the mice after vaccination with Ad-S1, suggesting that the adenovirus vaccine may aid the development of vaccines against SARS-CoV-2 and other genetically distinct viruses.
... The viral vector vaccine uses a modified version of a different virus (vector) that is safe as a vehicle to deliver specific instructions to patient muscle cells. The vector will use the cell's machinery to synthesize a harmless piece spike protein or corona spike protein, made up of the S1 subunit consisting of the receptor-binding domain and the S2 subunit consisting of a transmembrane anchor 8 . Similar to the mRNA vaccine, cells will display the spike proteins on their surface, allowing recognition by the immune system to trigger immunological responses to generate specific antibodies against the infection. ...
COVID-19 vaccines were designed to stimulate an immunological response, producing neutralizing antibodies against the SARS-CoV-2 spike protein. Vaccine variants such as mRNA, viral vector, whole-cell inactivated virus, and protein subunit vaccines, have been reported to be efficacious in phase III trials and have gained emergency use approval in many countries. However, several adverse effects are reported in certain types of vaccines. All vaccines are being expedited by some Asian countries as part of their national immunization programs. This review primarily discussed the selected manufacturers of the COVID-19 vaccines used and their effectiveness in early-adopting Asian countries. The effectiveness in reducing the infection rate and safety of COVID-19 vaccines in Japan, Thailand, Singapore and Malaysia was also analyzed based on the available data. Strategies that can be used to speed up the vaccination rate in reducing the number of COVID-19 cases were also evaluated.
... After the cleavage of spike protein S1, the S2 begins the process of viral fusion and lysosomal membrane. The severity of infection is attributed to spike proteins of these viruses as a result of the genetic alteration of the viruses; however, this is why the spike protein becomes the main target in developing antiviral drugs, monoclonal antibodies, and vaccines 29 . Approaches such as the inhibition of spikes protein from binding to its specific receptor on the target cell or using receptor antagonists will be useful in preventing attachment by the spike protein. ...
Enveloped viruses especially Coronaviruses, Influenza viruses, and Human Immunodeficiency viruses pose a great risk to the human and animal populations. These viruses cause diseases of clinical and socio-economic importance with the help of their spike protein. Coronaviruses affect the respiratory, gastrointestinal tract, and nervous system and the influenza virus affects the respiratory system while the Human Immunodeficiency Virus affects multiple systems as it invades and destroys immune cells. We aimed to review the role of spike protein in the four viruses and their effects on disease severity. We searched through online publication databases such as PubMed, Google Scholar, and Scopus to retrieve 150 scientific published articles using keywords like ‘Spike Protein’, ‘Viruses’, ‘Infection’, and ‘Diseases’. A total of 100 articles were used to write this article. Spike protein is an essential structure in viruses that causes infections and diseases in humans and animals. Targeting this protein in the development of antiviral drugs and vaccines should be a major concern.
... Current studies showed harmful effects of spike protein, including TLR activation, endothelial damage, SARS-CoV-2 entry into target cells, proinflammatory cytokine release, microglia stimulation, and molecular mimicry with heat shock proteins and chaperones. Therefore, it is reasonable to consider developing treatment that prevents the deleterious effects of spike proteins by using liposomal formulations of the natural flavonoids luteolin and methoxyluteolin in addition to existing vaccines and anti-inflammatory drugs 170,171 . ...
The pandemic of coronavirus disease 2019 (COVID-19) continuously causes deaths worldwide, representing a considerable challenge to health care and economic systems with a new precedent in human history. Many therapeutic medicines primarily focused on preventing severe organ damage and complications, which can be fatal in some confirmed cases. The synthesized modified mRNA (modRNA) represents a nonviral, integration-free, zero-footprint, efficient, and safe strategy for vaccine discovery. modRNA-based technology has facilitated the rapid development of the first COVID-19 vaccines due to its cost- and time-saving properties, thus initiating a new era of prophylactic vaccines against infectious diseases. Recently, COVID-19 modRNA vaccines were approved, and a large-scale vaccination campaign began worldwide. To date, results suggest that the modRNA vaccines are highly effective against virus infection, which causes COVID-19. Although short-term studies have reported that their safety is acceptable, long-term safety and protective immunity remain unclear. In this review, we describe two major approved modRNA vaccines and discuss their potential myocarditis complications.
... COVID vaccines do not deliver virus, but rather the RNA blueprint to make spike protein. SARS-CoV2 spike protein circulates after vaccination [18], and it is likely responsible for the serious reactions and deaths after COVID-19 vaccination [19]. The spike protein of SARS-CoV-2 virus alone (by itself) can damage vascular endothelial cells by downregulating ACE2 receptors and consequently inhibiting mitochondrial function [20]. ...
Chemtrails and Covid-19, two faces of Evil, threaten all life on our planet solely for political reasons. If we are to have a viable future on this planet, a critical mass of humanity must wake up to the atrocities of the ongoing chemtrail and biological operations. People must break out of their mass formation hypnosis and distractions, start to look up, and bear witness to the terrible suffering of the natural world around us. We are not separate entities from the rest of the biosphere: if the forests die, the wildlife dies, and the oceans die, we too will die. Our time is short – action is urgently needed now to salvage what remains of our natural life support systems and give our children a healthy and viable future.
... This happened even after the virus was no longer linked to the protein (Avolio et al., 2021b;Khaddaj-Mallat et al., 2021). Furthermore, nearly all mRNA-based vaccines now use the spike protein as the primary immunogen, and side effects from spike protein-based vaccine complications are beginning to pile up in the literature (Candelli et al., 2021;Kircheis, 2021;Theoharides and Conti, 2021;Wise, 2021). More evidence is needed to understand the cause of vaccineinduced immune thrombotic thrombocytopenia (VITT), with some researchers pointing to the spike protein as a significant contributor, while others disagree. ...
There is currently no antiviral proven to successfully combat COVID-19. Tackling the disease require halting virus proliferation and reducing viral complications in humans. The goal of this research is to evaluate the possible use of papaya leaves extract as a multifaceted antiviral and potential therapy for COVID-19. SARS–CoV–2 viral targets were nucleocapsid, main protease (Mpro), RNA dependent RNA polymerase, and spike protein (Wuhan, Delta, and Omicron variants) while TNF-alpha and alpha thrombin were the human targets evaluated. Comparisons with commercial repurposed drugs and phytochemicals from other plants were also made. The Autodock software was used for the molecular docking, and Gromacs was used for the molecular dynamics simulations. Before docking, the ligands were converted to 3D format and their energy was minimised. The free energies of binding for the SARS–CoV–2 targets RNA binding domain of nucleocapsid, main protease (Mpro), RNA dependent RNA polymerase, and spike protein (Wuhan, Delta, and Omicron variants) with protodioscin, the best PLE compound were –13.83, –13.19, –11.62, –11.19 (Wuhan), –11.57 (Delta), and –10.77 (Omicron), respectively. TNF–alpha and alpha–thrombin binding free energies were –13.64 and –13.50 kcal/mol, respectively. PLE compounds formed the majority of the top free energies of binding in all protein targets. The calculated inhibition constants for protodioscin, the best PLE compound in complex with Mpro, alpha thrombin, Nucleocapsid protein and TNF–alpha were in the picomolar range at 16.34, 27.07, 73.28 and 99.93 pM, respectively, whilst RdRp and spike protein (Omicron) were in the nanomolar range at 3.02 and 12.84 nM, respectively. Protodioscin interacted with key residues involved in catalytic activities or binding interactions with residues that have been reported in other docking studies for all protein targets. The binding affinity poses were confirmed by molecular dynamics simulation using root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses. Compounds from PLE especially protodioscin are probably the best in combating COVID-19 by tackling the virus and human sides simultaneously.
... As we continue to ensure appropriate access to COVID-19 mRNA vaccinations, it is as important to know which groups or individuals may not be such candidates. Neurological issues from vaccination may be the direct toxic effect of S-spike proteins as it damages the blood-brain barrier and can lead to immune dysregulation processes [9]. We also know tinnitus is not an exclusively auditory problem but may result from neurological changes within the auditory system and has been known to have neurological etiology from peripheral and central cytokine-mediated responses [10,11]. ...
With the worldwide goal of ending the pandemic, mRNA vaccines have been introduced as a valuable tool to help achieve both herd immunity and protect the most vulnerable. Neurological side effects from such vaccines have been increasingly documented, but to date, they are still deemed rare with no caution advised per the Centers for Disease Control and Prevention (CDC). As more of the younger population (under 40) are getting vaccinated according to recent approval and CDC recommendations, the real-world safety reporting data on adverse events have yet had time to catch up. We present three distinct neurological events that occurred after the Pfizer mRNA vaccine (BioNTech, Mainz, Germany), without identifiable alternate etiologies, in patients with an average age of 36 years presenting to an urban Florida clinic, all within eight weeks of one another. The presented cases occurred within hours of the second dose and, in one case, after the third booster dose of the Pfizer mRNA vaccine. These cases illustrate rising concerns of risks in widely recognized very low-risk age categories. A clearly delineated risk-benefit strategy likely needs to be implemented.
... Furthermore, experimental data show the entrance of the spike protein in cardiac pericytes and pulmonary vascular cells, which promotes cell signaling leading to vascular cell dysfunction and cell growth/hypertrophy [28,29]. It seems extremely interesting to be able to detect spike protein levels in plasma [30,31], but to the best of our knowledge, no practical, clinical use has been implemented thus far while these techniques are not widely available for use to investigate whether there is an association between the observed changes in endothelial function and the spike levels in plasma [32]. On the other hand, the triggering of the inflammatory cascade itself might adversely affect vascular function. ...
To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.
... The Spike protein has been suspected to have more effects than its common signature. It was reported by a paper that the Spike protein could change its shape to make it prone to bind to more cells, and some other papers show that it itself can harm endothelial cells and can disturb the blood-brain barrier (36). Due to the Spike protein having a major role in the SARS-CoV-2 disease, for the Alpha and Beta Indonesian variants, the mutations in the S gene will be focused on to be analyzed. ...
Background: SARS-CoV-2 virus is the cause of the global pandemic since the end of the year 2019. Since then, the virus has had mutations that cause different types of variants with various effects on those infected. This has complicated human intervention for prevention. Indonesia is one of the countries which was heavily affected by the pandemic specifically from May to August 2021, and it is a country that has recorded many distinct isolates.
Methods: GISAID database was used to obtain the Indonesian isolates while NCBI BLAST was utilized for comparison of all variants, and MAFFT version 7 for multi comparison.
Results: There were 9,488 isolates in Indonesia as of November 2021 where most include the Delta variant. Most of the isolates have mutations common to the ones from other countries. Although there are some atypical ones such as the mutation V1264L in the Delta variant that was suspected play a role in worsening the pandemic.
Conclusions: The Delta variant had the most mutations in the Spike protein, when compared to the Alpha and Beta variants, giving its important roles in infectivity and vigorous entry into cells, explaining why in the period of May to November 2021 in Indonesia, there was a rocket of cases for the Delta variant unlike the other variants
... However, two other papers reported negligible transmission [75,76]. However, transmission may not be required for the virus to induce neuroinflammation, as it may affect peripheral nerves [77] or the developing brain via the Spike protein directly affecting brain cells [78]. ...
The prevalence of autism spectrum disorder (ASD) continues to increase, but no distinct pathogenesis or effective treatment are known yet. The presence of many comorbidities further complicates matters, making a personalized approach necessary. An increasing number of reports indicate that inflammation of the brain leads to neurodegenerative changes, especially during perinatal life, “short-circuiting the electrical system” in the amygdala that is essential for our ability to feel emotions, but also regulates fear. Inflammation of the brain can result from the stimulation of mast cells—found in all tissues including the brain—by neuropeptides, stress, toxins, and viruses such as SARS-CoV-2, leading to the activation of microglia. These resident brain defenders then release even more inflammatory molecules and stop “pruning” nerve connections, disrupting neuronal connectivity, lowering the fear threshold, and derailing the expression of emotions, as seen in ASD. Many epidemiological studies have reported a strong association between ASD and atopic dermatitis (eczema), asthma, and food allergies/intolerance, all of which involve activated mast cells. Mast cells can be triggered by allergens, neuropeptides, stress, and toxins, leading to disruption of the blood–brain barrier (BBB) and activation of microglia. Moreover, many epidemiological studies have reported a strong association between stress and atopic dermatitis (eczema) during gestation, which involves activated mast cells. Both mast cells and microglia can also be activated by SARS-CoV-2 in affected mothers during pregnancy. We showed increased expression of the proinflammatory cytokine IL-18 and its receptor, but decreased expression of the anti-inflammatory cytokine IL-38 and its receptor IL-36R, only in the amygdala of deceased children with ASD. We further showed that the natural flavonoid luteolin is a potent inhibitor of the activation of both mast cells and microglia, but also blocks SARS-CoV-2 binding to its receptor angiotensin-converting enzyme 2 (ACE2). A treatment approach should be tailored to each individual patient and should address hyperactivity/stress, allergies, or food intolerance, with the introduction of natural molecules or drugs to inhibit mast cells and microglia, such as liposomal luteolin.
... This happened even after the virus was no longer linked to the protein (Avolio et al., 2021b;Khaddaj-Mallat et al., 2021). Furthermore, nearly all mRNA-based vaccines now use the spike protein as the primary immunogen, and side effects from spike protein-based vaccine complications are beginning to pile up in the literature (Candelli et al., 2021;Kircheis, 2021;Theoharides and Conti, 2021;Wise, 2021). More evidence is needed to understand the cause of vaccine-induced immune thrombotic thrombocytopenia (VITT), with some researchers pointing to the spike protein as a significant contributor, while others disagree. ...
The emergence of a new variant that can overcome the effectiveness of current vaccines is a real
threat that can jeopardize the eradication of COVID-19. This has prompt calls for
complementary treatments for combating the myriads of the COVID-19 disease spectrum. There
are 5 main hurdles for an effective COVID-19 treatment. The first is to inhibit viral replication.
The second is to simultaneously reduce the effects of cytokine storm that is initiated upon viral
infection. The third is to address the increasing case of hyperglycemic conditions in diabetic and
non-diabetic, the latter of which has been linked to SARS-CoV-2 infection of pancreatic cells.
Hyperglycemic conditions coupled with a lowering of immunity and steroids application may be
linked to the increasing incidence of black fungus infection. The fourth is to combat the
hypercoagulation related to venous and arterial thrombotic complications and the final fifth is to
restore platelet level after a thrombocytopenic event commonly seen in severe COVID-19
patients. To address these issues using drugs or medication within the short critical COVID-19
“storm” would require the use of a multidrug/medication approach where each component of the
medication would have its safety and efficacy issues as is seen in the current scenario. We are
proposing the use of the papaya leaves extract (PLE) as a complementary alternative medicine
that fulfils nearly all of the requirements above. PLE has undergone several clinical trials for the
dengue disease involving more than 1000 patients with overwhelming efficacy and safety
outcomes. In addition, the papaya plant is one of the most recognized plants globally. Aside from
the fruit, the leaves have been consumed for hundreds of years as medicine, food and drinks
showcasing the safety of PLE.
Background:
The rapid development of COVID-19 vaccines, combined with a high number of adverse event reports, have led to concerns over possible mechanisms of injury including systemic lipid nanoparticle (LNP) and mRNA distribution, Spike protein-associated tissue damage, thrombogenicity, immune system dysfunction, and carcinogenicity. The aim of this systematic review is to investigate possible causal links between COVID-19 vaccine administration and death using autopsies and post-mortem analysis.
Methods:
We searched PubMed and ScienceDirect for all published autopsy and necropsy reports relating to COVID-19 vaccination up until May 18th, 2023. All autopsy and necropsy studies that included COVID-19 vaccination as an antecedent exposure were included. Because the state of knowledge has advanced since the time of the original publications, three physicians independently reviewed each case and adjudicated whether or not COVID-19 vaccination was the direct cause or contributed significantly to death.
Results:
We initially identified 678 studies and, after screening for our inclusion criteria, included 44 papers that contained 325 autopsy cases and one necropsy case. The mean age of death was 70.4 years. The most implicated organ system among cases was the cardiovascular (49%), followed by hematological (17%), respiratory (11%), and multiple organ systems (7%). Three or more organ systems were affected in 21 cases. The mean time from vaccination to death was 14.3 days. Most deaths occurred within a week from last vaccine administration. A total of 240 deaths (73.9%) were independently adjudicated as directly due to or significantly contributed to by COVID-19 vaccination, of which the primary causes of death include sudden cardiac death (35%), pulmonary embolism (12.5%), myocardial infarction (12%), VITT (7.9%), myocarditis (7.1%), multisystem inflammatory syndrome (4.6%), and cerebral hemorrhage (3.8%).
Conclusions:
The consistency seen among cases in this review with known COVID-19 vaccine mechanisms of injury and death, coupled with autopsy confirmation by physician adjudication, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death. Further urgent investigation is required for the purpose of clarifying our findings.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that poses a serious threat to global public health. In an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike (S) protein to engage with angiotensin-converting enzyme 2 (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, with luteolin being a flavonoid that can significantly inhibit SARS-CoV infection. However, whether it can block the interaction between the S-protein RBD of SARS-CoV-2 and ACE2 has not yet been elucidated. Here, we investigated the effects of luteolin on the binding of the S-protein RBD to ACE2. By employing a competitive binding assay in vitro, we found that luteolin significantly blocked the binding of S-protein RBD to ACE2 with IC50 values of 0.61 mM, which was confirmed by the neutralized infection with SARS-CoV-2 pseudovirus in vivo. A surface plasmon resonance-based competition assay revealed that luteolin significantly affects the binding of the S-protein RBD to the ACE2 receptor. Molecular docking was performed to predict the binding sites of luteolin to the S-protein RBD-ACE2 complex. The active binding sites were defined based on published literature, and we found that luteolin might interfere with the mixture at residues including LYS353, ASP30, and TYR83 in the cellular ACE2 receptor and GLY496, GLN498, TYR505, LEU455, GLN493, and GLU484 in the S-protein RBD. These residues may together form attractive charges and destroy the stable interaction of S-protein RBD-ACE2. Luteolin also inhibits SARS-CoV-2 spike protein-induced platelet spreading, thereby inhibiting the binding of the spike protein to ACE2. Our results are the first to provide evidence that luteolin is an anti-SARS-CoV-2 agent associated with interference between viral S-protein RBD-ACE2 interactions.
SARS-CoV2 is a novel respiratory coronavirus and, understanding its molecular mechanism is a prerequisite to developing effective treatment for covid-19. This RNA genome-carrying virus has a protein coat with spikes (S) that attaches to the ACE2 receptor at the cell surface of human cells. Several repurposed drugs are used to treat covid-19 patients that are proven to be largely unsuccessful or have limited success in reducing mortalities. Several vaccines are in use to reduce the viral load to prevent developing symptoms. Major challenges to their efficacy include the inability of antibody molecules to enter cells but remain effective in the bloodstream to kill the virus. The efficacy of vaccines also depends on their neutralizing ability to constantly evolve new virus strains due to novel mutations and evolutionary survival dynamics. Taken together, SARS-CoV2 antibody vaccines may not be very effective and other approaches based on genetic, genomic, and protein interactome could be fruitful to identify therapeutic targets to reduce disease-related mortalities.
Background
The COVID-19 period highlights a huge problem that has been developing for decades, the control of science by industry. In the 1950s, the tobacco industry set the example, which the pharmaceutical industry followed. Since then, the latter has been regularly condemned for illegal marketing, misrepresentation of experimental results, dissimulation of information about the dangers of drugs, and considered as criminal. Therefore, this study was conducted to show that knowledge is powerfully manipulated by harmful corporations, whose goals are: 1/financial; 2/to suppress our ability to make choices to acquire global control of public health.
Methods
Pharmaceutical industry techniques for manipulating science and COVID-19 reporting were reviewed. Several sources of official documents were used: PubMed; National Institutes of Health resources; pharmaceutical companies; policy documents; national newspapers and news agencies; and books by prominent professionals (scientific and legal). A few studies have not been published in peer-reviewed journals; however, they have been conducted by reputable scientists in their respective fields.
Results
Since the beginning of COVID-19, we can list the following methods of information manipulation which have been used: falsified clinical trials and inaccessible data; fake or conflict-of-interest studies; concealment of vaccines’ short-term side effects and total lack of knowledge of the long-term effects of COVID-19 vaccination; doubtful composition of vaccines; inadequate testing methods; governments and international organizations under conflicts of interest; bribed physicians; the denigration of renowned scientists; the banning of all alternative effective treatments; unscientific and liberticidal social methods; government use of behavior modification and social engineering techniques to impose confinements, masks, and vaccine acceptance; scientific censorship by the media.
Conclusion
By supporting and selecting only the one side of science information while suppressing alternative viewpoints, and with obvious conflicts of interest revealed by this study, governments and the media constantly disinform the public. Consequently, the unscientifically validated vaccination laws, originating from industry-controlled medical science, led to the adoption of social measures for the supposed protection of the public but which became serious threats to the health and freedoms of the population.
In a given country, we have the set of alive people and the subset of vaccinated people. During a period of 4 weeks, some people that are Covid-19 positive died. Thus, we have another set of Covid-19 positive dead persons that has as its subset Covid-19 positive dead vaccinated persons. We will compare the statistical number of Covid-19 positive dead vaccinated persons with the proportional number of Covid-19 positive dead vaccinated persons, valid in case the vaccines do not affect health. The proportional number must be always bigger than the number of Covid-19 positive dead vaccinated persons provided by official statistical data. In this case, covid vaccines are safe and efficient in saving human lives.
Background
We investigated the frequency of brain fog in a large cohort of patients with documented COVID-19 who have survived the illness. We also scrutinized the potential risk factors associated with the development of brain fog.
Methods
Adult patients (18-55 years of age), who referred to the healthcare facilities anywhere in Fars province from 19 February 2020 until 20 November 2020 were included. All patients had a confirmed COVID-19 diagnosis. In a phone call, at least three months after their discharge from the hospital, we obtained their current information. A questionnaire was specifically designed for data collection.
Results
In total, 2,696 patients had the inclusion criteria; 1,680 (62.3%) people reported long COVID syndrome. Long COVID syndrome-associated brain fog was reported by 194 (7.2%) patients. Female sex (odds ratio: 1.4), respiratory problems at the onset (odds ratio: 1.9), and ICU admission (odds ratio: 1.7) were significantly associated with reporting chronic post-COVID “brain fog” by the patients.
Conclusion
Long COVID syndrome is a frequent and significant condition. In this large population based study, we report that chronic post-COVID “brain fog” has significant associations with sex (female), respiratory symptoms at the onset, and the severity of the illness (ICU admission).
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The COVID-19 pandemic made imperative the search for means to end it, which requires a knowledge of the mechanisms underpinning the multiplication and spread of its cause, the coronavirus SARS-CoV-2. Many viruses use members of the hosts’ chaperoning system to infect the target cells, replicate, and spread, and here we present illustrative examples. Unfortunately, the role of chaperones in the SARS-CoV-2 cycle is still poorly understood. In this review, we examine the interactions of various coronaviruses during their infectious cycle with chaperones in search of information useful for future research on SARS-CoV-2. We also call attention to the possible role of molecular mimicry in the development of autoimmunity and its widespread pathogenic impact in COVID-19 patients. Viral proteins share highly antigenic epitopes with human chaperones, eliciting anti-viral antibodies that crossreact with the chaperones. Both, the critical functions of chaperones in the infectious cycle of viruses and the possible role of these molecules in COVID-19 autoimmune phenomena, make clear that molecular chaperones are promising candidates for the development of antiviral strategies. These could consist of inhibiting-blocking those chaperones that are necessary for the infectious viral cycle, or those that act as autoantigens in the autoimmune reactions causing generalized destructive effects on human tissues.
Research in animals and humans has indicated that polyphenols can delay the age-related decline in learning, memory and neurodegenerative diseases. Among the polyphenols, berry phenolics have extensive beneficial effects because of their antioxidant and anti-inflammatory properties. Long-term consumption of grapes results in accumulation of polyphenols in the brain, which modulates cell-signalling pathways and neutralises the redox imbalance in the aging brain. Here we review the in vivo and in vitro evidence for considering grape-derived polyphenolics, the flavonoids- catechins, epicatechin, anthocyanidin, and quercetin, and non-flavonoids-gallic acid and resveratrol, as effective dietary sources to facilitate cognition in adults and lessen the decline in the old and pathogenic states, Alzheimer’s and Parkinson’s disease. Furthermore, a combined intervention of polyphenols along with regular physical exercise provides cognitive benefits for the aging brain and holds promising venues for preclinical and clinical studies in formulating neuro-nutraceuticals as functional foods for a healthy brain.