Spike protein

The spike protein of SARS-CoV-2 has been found to exhibit pathogenic characteristics and be a possible cause of post-acute sequelae after SARS-CoV-2 infection or COVID-19 vaccination. COVID-19 vaccines utilize a modified, stabilized prefusion spike protein that may share similar toxic effects with its viral counterpart. The aim of this study is to investigate possible mechanisms of harm to biological systems from SARS-CoV-2 spike protein and vaccine-encoded spike protein and to propose possible mitigation strategies. We searched PubMed, Google Scholar, and 'grey literature' to find studies that (1) investigated the effects of the spike protein on biological systems, (2) helped differentiate between viral and vaccine-generated spike proteins, and (3) identified possible spike protein detoxification protocols and compounds that had signals of benefit and acceptable safety profiles. We found abundant evidence that SARS-CoV-2 spike protein may cause damage in the cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems. Viral and vaccine-encoded spike proteins have been shown to play a direct role in cardiovascular and thrombotic injuries from both SARS-CoV-2 and vaccination. Detection of spike protein for at least 6-15 months after vaccination and infection in those with post-acute sequelae indicates spike protein as a possible primary contributing factor to long COVID. We rationalized that these findings give support to the potential benefit of spike protein detoxification protocols in those with long-term postinfection and/or vaccine-induced complications. We propose a base spike detoxification protocol, composed of oral nattokinase, bromelain, and curcumin. This approach holds immense promise as a base of clinical care, upon which additional therapeutic agents are applied with the goal of aiding in the resolution of postacute sequelae after SARS-CoV-2 infection and COVID-19 vaccination. Large-scale, prospective, randomized, double-blind, placebo-controlled trials are warranted in order to determine the relative risks and benefits of the base spike detoxification protocol.

The spike protein (S-protein) of SARS-CoV-2 plays an important role in binding, fusion, and host entry. In this study, we have predicted interatomic bond strength between receptor binding domain (RBD) and angiotensin converting enzyme-2 (ACE2) using machine learning (ML), that matches with expensive ab initio calculation result. We collected bond order result from ab initio calculations. We selected a total of 18 variables such as bond type, bond length, elements and their coordinates, and others, to train ML models. We then trained five well-known regression models, namely, Decision Tree regression, KNN Regression, XGBoost, Lasso Regression, and Ridge Regression. We tested these models on two different datasets, namely, Wild type (WT) and Omicron variant (OV). In the first setting, we used 90% of each dataset for training and 10% for testing to predict the bond order. XGBoost model outperformed all the other models in the prediction of the WT dataset. It achieved an R2 Score of 0.997. XGBoost also outperformed all the other models with an R2 score of 0.9998 in the prediction of the OV dataset. In the second setting, we trained all the models on the WT (or OV) dataset and predicted the bond order on the OV (or WT) dataset. Interestingly, Decision Tree outperformed all the other models in both cases. It achieved an R2 score of 0.997.

The recent outbreak of a new coronavirus disease known as COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a highly contagious and pathogenic viral infection that has spread worldwide. Coronaviruses are known to cause disease in humans, other mammals, and birds. Although specific therapeutics and vaccines require efforts in this direction, reaching the world's population with mutations of the virus can be a difficult target. The major proteases of coronavirus play a critical role during the spread of the disease and therefore still represent an important target for drug discovery. As of now, there is still no official treatment for infected patients. In this study, bioinformatics-based molecular docking studies were performed to identify potent inhibitors of novel candidate molecules against the spike protein S of SARS-CoV-2. The affinities of ligand molecules thought to be effective in the treatment of SARS-CoV-2 disease were investigated. For this purpose, 1,615 different FDA-approved drug ligand molecules were retrieved from ZINC15 database. Crystallographic structure of spike protein S of SARS-CoV-2 was retrieved from Protein Data Bank (PDB). Initial virtual screening was performed using qvina-w, an accelerated version of AutoDock Vina optimized for rapid docking, to evaluate binding affinities of all 1,615 compounds against the spike protein. The top 10 ligands with the most favorable binding affinities were selected for further analysis. These ligands were docked to the target protein with Autodock Vina. The complexes were first solvated and then run through Molecular Dynamics (MD) simulations, utilizing NAMD. The binding energies were computed through these interactions, which are used to compare the affinities of the ligands to the target protein. Ultimately, 10 different ligands

Famotidine is of interest as a possible treatment for COVID-19, with effects on disease-related symptoms and survival reported in observational and retrospective studies, as well as in silico predictions of binding to potential SARS-CoV-2 drug targets. Published studies of famotidine for COVID-19 have focused on acute illness, and none have reported on neuropsychiatric symptoms. This case study reports on an 18-year-old man who sought psychiatric treatment for depression and anxiety, disruptive interpersonal conflicts, and impairments in attention and motivation following mildly symptomatic illness with COVID-19. The neuropsychiatric symptoms, which had been present for 16 weeks at the time of the initial evaluation represented a significant departure from the patient's previous behavioral baseline. The patient had no prior psychiatric history preceding his illness with COVID-19, and no history of any prior treatment with psychopharmacological medications. Famotidine 20 mg twice daily administered orally was begun without any additional medications. At 1-week follow-up the patient was much improved. Improvement was sustained through 12 weeks of follow-up during which the patient continued to take famotidine without apparent side effects. With progression of the COVID-19 pandemic it has become evident that persistent disease-related symptoms may follow acute COVID-19 and may include neuropsychiatric symptoms. Controlled clinical research on famotidine for COVID-19 should follow, as well as the development of valid and reliable research diagnostic criteria to define and operationalize the features of a putative COVID-19 neuropsychiatric residual.

Keywords: COVID-19; SARS-CoV-2; anxiety; cognitive; depression; famotidine (FAM); neuroinflammation; psychiatry.

El “exposoma” abarca la diversidad de exposiciones a químicos sintéticos, medicamentos, dieta, factores psicosociales, físicos, y sus respuestas biológicas y afectación en la salud. Caracterizar el exposoma es un esfuerzo comparable al del genoma humano y se le queda grande a las políticas de salud ambiental. Estas exposiciones, incluso prenatales, generan una carga tóxica sistémica, pérdida de homeostasis, afectación genética y epigenética, y disrupciones endocrinas, alterando el eje Psico-Inmuno-Neuro-Endocrino (PINE) y provocando patologías multisistémicas complejas. La Medicina Ambiental (MA), nacida en los años 70, y el llamamiento de las instituciones sanitarias al problema de salud ambiental, otorgan a la Enfermería Ambiental (EA) un papel crucial en la prevención, diagnóstico precoz y cuidados. El metaparadigma enfermero es esencial para la relación dinámica entre paciente y estructuras de cuidado. La creación de una consulta funcional de EA es clave para enfrentar problemas de salud ambiental y garantizar la sostenibilidad del sistema sanitario.
Palabras clave: Enfermería ambiental. Medicina Ambiental. Exposoma. Medio Ambiente. Sensibilidad Química Múltiple. Electrohipersensibilidad.

This article introduces a new paradigm in nutritional science for long-term weight management, based on the integration of bioneurofeedback and bioimpedance analysis. Bioneurofeedback, a technique that combines the monitoring of physiological parameters with the modulation of brain activity, is employed to improve the self-regulation of eating behaviors by adjusting brainwave activity and reducing stress. Bioimpedance analysis provides a precise evaluation of body composition, enabling the personalization of interventions according to individual physiological and metabolic characteristics. This integrated approach utilizes the principles of cybernetics and complex systems theory to better understand the interaction between mind and body, enhancing weight regulation through a dual top-down and bottom-up strategy. Additionally, the article discusses how an excess or deficiency in specific brainwaves can affect disordered eating behaviors, proposing biofeedback integration as a method to mitigate the yo-yo effect and promote sustainable lifestyle changes.

Background: SARS-CoV-2 is a highly contagious virus that elicits COVID-19, a respiratory illness with a range of symptoms that can progress systemically and prove fatal. Vaccine development against the virus has been a crucial advance in combatting the pandemic, with vaccine efficacy being evaluated through analysis of antibody response. However, the magnitude of antibody response varies by vaccine and individual immunological status. Although even suboptimal antibody response may provide protection, COVID-19 immunity is a multi-factorial process that includes other immune components.

Objective: To measure changes in IgGSP antibody levels in response to the COVID-19 Sputnik vaccine, as analyzed by three serum samples collected at different time points in both seropositive and seronegative individuals.

Methods: A pre-post interventional study was carried on 324 military HCWs administering the Sputnik Vaccine at the Military Central COVID-19 Vaccination Unit from March till the end of July 2021.

Results: Participants were divided into seropositive and seronegative groups based on SARS-CoV-2 antibody levels. The seropositive group had a greater increase in IgGSP antibody titer after one vaccine dose. Both groups showed a significant decline in IgGSP levels after 12 weeks of complete vaccination, but the decline was less prominent in the seropositive group. This suggests the need for booster doses every six months to strengthen the immune system after the decline.

Conclusion: IgGSP antibodies are effective against SARS-CoV-2, but the minimum level for protection is unclear and requires further research to establish a cut-off point.

Background: Listeria monocytogenes, a Gram-positive bacterium, is a prominent foodborne pathogen that causes listeriosis and poses substantial health hazards worldwide. The continuing risk of listeriosis outbreaks underlies the importance of designing an effective prevention strategy and developing a robust immune response by reverse vaccinology approaches. This study aimed to provide a critical approach for developing a potent multiepitope vaccine against this foodborne disease. Methods: A chimeric peptide construct containing 5 B-cell epitopes, 16 major histocompatibility complex I (MHC-I) epitopes, and 18 MHC-II epitopes were used to create a subunit vaccination against L. monocytogenes. The vaccine safety was evaluated by several online methods, and molecular docking was performed using ClusPro to determine the binding affinity. Immune simulation was performed using the C-ImmSimm server to demonstrate the immune response. Results: The results validated the antigenicity, non-allergenicity, and nontoxicity of the chimeric peptide construct, confirming its suitability as a subunit vaccine. Molecular docking showed a good score of 1276.5 and molecular dynamics simulations confirmed the construct's efficacy, demonstrating its promise as a good candidate for listeriosis prophylaxis. The population coverage was as high as 91.04% with a good immune response, indicating good antigen presentation with dendritic cells and production of memory cells. Conclusions: The findings of this study highlight the potential of the designed chimeric peptide construct as an effective subunit vaccine against Listeria, paving the way for future advances in preventive methods and vaccine design.

Since its outbreak, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spread rapidly, causing the Coronavirus Disease 19 (COVID-19) pandemic. Even with the vaccines’ administration, the virus continued to circulate due to inequal access to prevention and therapeutic measures in African countries. Information about COVID-19 in Africa has been limited and contradictory, and thus regional studies are important. On this premise, we conducted a genomic surveillance study about COVID-19 lineages circulating in Bangui, Central African Republic (CAR). We collected 2687 nasopharyngeal samples at four checkpoints in Bangui from 2 to 22 July 2021. Fifty-three samples tested positive for SARS-CoV-2, and viral genomes were sequenced to look for the presence of different viral strains. We performed phylogenetic analysis and described the lineage landscape of SARS-CoV-2 circulating in the CAR along 15 months of pandemics and in Africa during the study period, finding the Delta variant a...

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Context: Coronavirus disease 2019 (COVID-19), a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic. Selenium derived from the plants of the Brassicaceae family plays an important role in several biological functions, often as an antioxidant or antiviral. In particular, selenium can be used as an adjuvant in the treatment of various viral infections. Aims: To determine the potential drug, as well as the affinity and the bond energy associated with chemical interaction bonds between the complex selenium compounds from Brassicaceae as inhibitors of the SARS-CoV-2 spike protein and MAP4 through the use of in silico studies. Methods: The methods used in this study consisted of receptor and ligand data collection, ADMET analysis, molecular docking, and molecular dynamics. Results: The results of this study indicate that the selenium complex compounds have the potential to be used as a spike inhibitor drug for SARS-CoV-2, as they have passed the Lipinski test and showed promise in the pharmacokinetic analysis. The results of the bond docking show that several complex selenium compounds, such as ethaselen, selenomethionine, and selenocystine, have stronger binding affinity values than the controls. This is compared to the control MAP4, which yielded binding affinities of-6.1 kcal/mol and spike protein-7 kcal/mol, respectively. Controlled bisoxatin and estramustine are drugs with mechanisms targeted to MAP4 and spike protein, which are the usual standards used. Conclusions: The similarity of sites, the binding of several amino acid residues dominated by hydrogen bonds, and the result of molecular dynamic results for the selenium compound derived from Brassicaceae showed a stable bond to the spike protein and MAP4 with low fluctuation levels.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, of long COVID. It can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence GPCR signalling in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, as well as the brain, are complex and require deep research to fully understand their implications for Long COVID-19 manifestation. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations.

Resumen Los Síndromes de Sensibilización Central (SSC) abarcan una serie de complejas patologías con variados síntomas multisistémicos persistentes, que presentan en común una neuroinflamación y consecuente sensibilización neural (del sistema nervioso central y periférico) que provoca en cascada un círculo vicioso neuro-endocrino-inmunológico, quedando huérfanas de tratamientos. Las últimas líneas de investigación sobre SSC (SQM/SFC/EM) se dirigen a la similitud sintomatológica del Covid Persistente con estas patologías, postulándose en activaciones de retrovirus endógenos tras cuadros postvirales. La multivariabilidad sintomatológica persistente que provocan las terapias génicas ARNm ("Vacunas Covid"), pueden estar justificadas por los mecanismos de acción y características de éstas (no solo neuroinflamatorios, neurotóxicas, y neurosensibilizantes de ciertos NLP, sino también de la inserción del ARNm sintético al genoma huésped) y su similitud en la fisiopatología de los SSC y sus características. Con los datos y reportes que tenemos hasta ahora, no parece seguro que los pacientes de SSC puedan recibir sin inocuidad las terapias génicas.

Palabras clave: Síndromes de Sensibilización Central. Vacunas Covid. Neuroinflamación. Covid Persistente.

Crimean-Congo hemorrhagic fever (CCHF) is a highly severe and virulent viral disease of zoonotic origin, caused by a tick-born CCHF virus (CCHFV). The virus is endemic in many countries and has a mortality rate between 10% and 40%. As there is no licensed vaccine or therapeutic options available to treat CCHF, the present study was designed to focus on application of modern computational approaches to propose a multi-epitope vaccine (MEV) expressing antigenic determinants prioritized from the CCHFV genome. Integrated computational analyses revealed the presence of 9 immunodominant epitopes from Nucleoprotein (N), RNA dependent RNA polymerase (RdRp), Glycoprotein N (Gn/G2), and Glycoprotein C (Gc/G1). Together these epitopes were observed to cover 99.74% of the world populations. The epitopes demonstrated excellent binding affinity for the B- and T-cell reference set of alleles, the high antigenic potential, non-allergenic nature, excellent solubility, zero percent toxicity and inter...

Microscale thermophoresis (MST) is an analytical technique for measuring biomolecular interactions. It is based on the physical phenomenon that particles move within temperature gradients, which is affected by their size, charge, hydration shell and conformation. The MST sample must contain a fluorescent target molecule used to observe the movement of particles, and this can be titrated with an unlabelled binding partner for quantifying the interaction. MST is highly sensitive, using relatively small amounts of sample, and it has no limitations on the size of the target biomolecule, on the affinity of the interaction or on the composition of the buffer and other sample components. This makes MST ideally suited to characterising interactions with membrane proteins, which can be studied in cell lysates, native membranes, solubilised in detergents or reconstituted in lipids. The intrinsic aromatic residues of membrane proteins have been used as the fluorophore for MST (label-free MST) or membrane proteins have been labelled with a range of fluorescent dyes or conjugated with fluorescent proteins (labelled MST). The different types of membrane proteins that have had biomolecular interactions characterised by MST include the SARS-CoV-2 spike protein, GPCRs and other receptors, sensor kinases, ion channels, aquaporins, and transport proteins.

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week...

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week...

The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) continues to reshape the globe. It is more than a year since the virus first emerged, yet the vast majority of people are still vulnerable. The current response to the COVID-19 pandemic involves aggressive implementation of containment, suppression, and mitigation strategies causing devastating social, economic and political crises. The restrictions on our lives are the only thing holding the virus in check. The world cannot return to normal without safe and effective vaccines against COVID-19 along with a coordinated global vaccination program. Vaccines remain the safest, most cost-effective protection against disease. Unprecedented data sharing and collaborative team efforts are breaking down barriers in an attempt to reduce the time of vaccine development. An ideal COVID-19 vaccine should be safe, provide longlasting protection, protect not only against disease but prevent virus transmission to others, be able to be produced quickly and in large quantities, be easily stored, transported and administered. The global COVID-19 vaccine pipeline is currently expanding on a daily basis. Multiple platforms are being used for producing vaccines at pandemic speed. Each platform has its own merits, demerits and challenges and it is unlikely that any single platform on its own will constitute a solution for the ongoing COVID-19 pandemic.

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Background: The arboviruses Zika virus (ZIKV) is a pathogen that threatens human health. Scientists have warned that a single mutation in the mosquito-borne ZIKV could spark another major outbreak of the disease in humans. Therefore, designing a suitable vaccine for this virus seems necessary. This study aimed to predict the protective epitopes of envelope protein from the Zika virus with bioinformatics methods for multi-epitope vaccine development.
Materials and Methods: Computational studies including the identification of potential B-cell and T-cell epitopes were used. For generating a multi-epitopic vaccine construct (MEVC), selected epitopes are connected by suitable linkers. To enhance protein immunogenicity, Maltosebound protein was added to the MEVC after the prediction and refinement of the 3D structure of the designed vaccine. The binding mode of the MEVC with toll-like receptor was investigated by molecular docking technique. Finally, molecular dynamics and in silico cloning were performed for the designed vaccine.
Results: This study showed that this recombinant vaccine is nontoxic, nonallergenic, and thermostable and elicits immune responses against the Zika virus.
Conclusion: The computational data suggest that the MEVC has appropriate characteristics and a high-quality structure.

Palabras clave: vacunas; vasculitis; vacunas contra la COVID-19; evento adverso atribuible a la vacunación. RESUMEN Varios reportes comunicaron diferentes tipos de vasculitis en asociación temporal con una variedad de vacunas, y más recientemente con las vacunas para enfermedad por SARS-CoV-2 (COVID-19). Sin embargo, la escasez de estudios controlados y la heterogeneidad metodológica de los reportes no permiten una conclusión clara sobre su relación causal. Informamos el caso de un varón que desarrolló vasculitis leucocitoclástica, confirmada por biopsia de piel y sin compromiso sistémico, luego de la inmunización contra la COVID-19 con la vacuna de AstraZeneca.

Introduction: Coronavirus family member SARS-CoV-2 is a current worldwide threat. It enters into the epithelium membrane of respiratory tract with the help of its antigenic spike proteins and cause Coronavirus disease 2019 (COVID-19). Methods: Considering SARS-CoV-2 a potent vaccine or diagnostic candidate, a bioinformatical study was done to determine its structure homology modeling, physiological properties and structure validation with presence of antigenic sites. Results: The surface glycoprotein of SARS-CoV-2 was found to be a stable protein with stereochemically good structure. It also contains 65 antigenic sites. Conclusion: The present study suggests further wet-lab research to develop a vaccine or diagnostic kit using this promising surface glycoprotein.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur spontaneously during replication. Thousands of mutations have accumulated and continue to since the emergence of the virus. As novel mutations continue appearing at the scene, naturally, new variants are increasingly observed. Since the first occurrence of the SARS-CoV-2 infection, a wide variety of drug compounds affecting the binding sites of the virus have begun to be studied. As the drug and vaccine trials are continuing, it is of utmost importance to take into consideration the SARS-CoV-2 mutations and their respective frequencies since these data could lead the way to multi-drug combinations. The lack of effective therapeutic and preventive strategies against human coronaviruses (hCoVs) necessitates research that is of interest to the clinical applications. The reason why the mutations in glycoprotein S lead to vaccine escape is related to the location of the mutation and the affinity of the protein. At the same time, it can be said that variations should occur in areas such as the receptor-binding domain (RBD), and vaccines and antiviral drugs should be formulated by targeting more than one viral protein. In this review, a literature survey in the scope of the increasing SARS-CoV-2 mutations and the viral variations is conducted. In the light of current knowledge, the various disguises of the mutant SARS-CoV-2 forms and their apparent differences from the original strain are examined as they could possibly aid in finding the most appropriate therapeutic approaches.

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week...

Background: The research reports on a medical case of SARS-CoV-2 vaccinated patient. With the SARS-CoV's Spike 2 (S2) protein sharing similar helix structure with HIV-1 gp41, the patient experienced severe immune system responses one year after the third dose of Kexing recombined vaccines.

Methods: The author conceived a medicine induced hemodialysis technique according to the patient's symptoms, and implemented after emergent treatments. Indicators from the patient's emergent treatments corroborate with the initial prescription's validity.

Results: The clinical case validates the medicine induced hemodialysis method in treating SARS-CoV(-2)-related early symptoms in reducing irreversible damages to humans, depending on individual clinical cases.

Conclusions: The clinical case along with literature review suggests SARS-CoV series are compound virus unlikely from natural origins. It is inferred to have spread in mainland China at least back to the 1990s, and possibly a result from nuclear tests. The downplay of SARS-CoV-2's S2 protein and epidemiological varieties could have led to the global vaccine mandates, and the damages to human immune system need to be further researched into. The research concludes that SARS-CoV evidenced PRC's transgressions to the 1948 Geneva Conventions, which is the reason that the regime and its ruling party are systematically and willfully lying to the society and global institutions.

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 (severe
acute respiratory syndrome coronavirus 2) has posed an enigmatic challenge to global public health security. Current available vaccines are less
effective to prevent SARS-CoV-2 infections due to rapid rate mutations in his genome & it's also responsible for increased viral transmissibility
leads to morbidity & mortality. The aim of the present study to design a peptide vaccine against SARs-Cov-2 by using epitope (B-cell & T-cell)
based reverse vaccinology approach. The structural proteins Spike protein & Nucleoprotein of SARS-CoV-2 were used to identify potential
epitope to construct effective peptide vaccine which prevents SARS-CoV-2 infections. Various reverse vaccinology resources & tools such as
EXPASY, Vaxijen, IEDB, CTLPred, ALGPred, Pepfold and HPEPDOCK were used for immunoinformatics analysis. We investigated the
parameters associated with antigenicity, toxicity, and allergenicity of selected proteins by evaluating their various properties. The result obtained
from different steps of immunoinformatics analysis was satisfactory. The CTL epitopes that passed the antigenicity, allergenicity, toxigenicity, and
immunogenicity assessment were 02 epitopes from the nucleoprotein becomes effective & safer vaccine to prevent SARS-CoV-2 infections but the
experimental tests becomes essential to validate the efcacy of epitope based peptide vaccine.

Aim of this work is to search and analyze scientific literature involved in the effect played by wireless comunication radiation in the S.A.R.S-COV-2 spike protein derivates pathological process. This make possible to verify if it is necessary to be considered as a toxicological co-factor Various published evidence finded graphene impurity in vial some COVID-19 vaccine (P. Campra) or in vaccinated blood. But It is relevant to deeply investigate this phenomena using only scientifc evidence. Crucial also to verify the subpopulation distribution of pathological event in vaccinated like pericarditys or central nervous system thrombosys as well as the use of some technological tool like smartphone in the various age classes. This method make possible to generate hypotesys to be better veriefied. In this work is used a neutral approch without pre-concept.

Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782...

Adenovirus vectors have been employed to develop a vaccine against severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) for curtailing the Covid-19 pandemic spreading. Many different viral vectors have been mainly
targeting the SARS-CoV-2 spike (S) protein as an antigen. Spike (S) protein is comprised of S1 and S2 subunits, in
which the receptor-binding domain (RBD) of S1 is responsible for recognizing and engaging with its host cellular
receptor protein angiotensin-converting enzyme 2 (ACE2), S2 accounts for membrane fusion of virus and host cell.
Chimpanzee adenovirus was also used as a vector vaccine for SARS-CoV-2 (ChAdSARS-CoV-2-S) by
intramuscular injection, and intranasal administration has been tested. Adenovirus vector-based vaccines are the
most advanced, with several vaccines receiving Emergency Use Authorization (EUA). It was shown that rhesus
macaques were protected from SARS-CoV-2 challenge after a month of being vaccinated with ChAd-SARS-CoV-2-
S. A single intranasal or two intramuscular ChAd-SARSCoV-2-S vaccines could induce humoral antibodies and T cell
responses to protect the upper and lower respiratory tract against SARS-CoV-2. As the effectiveness was
demonstrated in non-human primates, ChAd-SARS-CoV-2-Sa potential option for preventing SARS-CoV-2
infection in humans. However, detecting novel more transmissible and pathogenic SARS-CoV-2 variants added
concerns about the vaccine efficacy and needs monitoring. Moreover, the cause of recently documented rare cases of
vaccine indicated immune thrombotic thrombocytopenia. This review article provided details for the adenovirus
vector vaccine for SARS-CoV-2 in humans and tried to provide solutions to the adenovirus vector hemagglutinin
issue.

Objective: At present, the coronavirus disease (COVID)-19 pandemic is increasing global health concerns. This coronavirus outbreak is caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. Since, no specific antiviral for treatment against COVID-19, so identification of new therapeutics is an urgent need. The objective of this study is to the analysis of lichen compounds against main protease and spike protein targets of SARS-CoV-2 using in silico approach. Methods: A total of 108 lichen compounds were subjected to ADMET analysis and 14 compounds were selected based on the ADMET properties and Lipinski's rule of five. Molecular docking was performed for screening of selected individual lichen metabolites against the main protease and spike proteins of SARS-CoV-2 by Schrodinger Glide module software. Results: Among the lead compounds, fallacinol showed the highest binding energy value of −11.83 kcal/mol against spike protein, 4-O-Demethylbarbatic acid exhibited the highest dock score of −11.67 kcal/mol against main protease. Conclusion: This study finding suggests that lichen substances may be potential inhibitors of SARS-CoV-2.

Background: New coronavirus disease is considered one of the most widely spreading viral infections all over the world. Increased numbers of severe covid-19 cases are growing up. Gene sequencing and discovering new viral variants is an essential aspect during the pandemic. The generation of treatment-resistant viral strains and the probability of negative impact on vaccination efficacy is possible. We aimed to review the probable effect of new variant emergence on treatment and vaccination efficacy, besides, the importance of gene sequencing from published literature data till the moment. Main body of the abstract: SARS-CoV-2 genome studies indicated that it shared 79 to 82% nucleotide similarity with SARS-CoV-1. Several gene locations in the envelope (E) structural protein c.222G>C (p. Leu74Leu) and the Membrane (M) structural protein c.213C>T (p. Tyr71Tyr) were proved to have mutations. Also, the surface (S) gene mutation c.1841A>G (p. Asp614Gly) is most relevant. The pub...

Syphilis, a sexually transmitted infection, is a deadly disease caused by Treponema pallidum. It is a Gram-negative spirochete that can infect nearly every organ of the human body. It can be transmitted both sexually and perinatally. Since syphilis is the second most fatal sexually transmitted disease after AIDS, an efficient vaccine candidate is needed to establish long-term protection against infections by T. pallidum. This study used reverse-vaccinology-based immunoinformatic pathway subtractive proteomics to find the best antigenic proteins for multi-epitope vaccine production. Six essential virulent and antigenic proteins were identified, including the membrane lipoprotein TpN32 (UniProt ID: O07950), DNA translocase FtsK (UniProt ID: O83964), Protein Soj homolog (UniProt ID: O83296), site-determining protein (UniProt ID: F7IVD2), ABC transporter, ATP-binding protein (UniProt ID: O83930), and Sugar ABC superfamily ATP-binding cassette transporter, ABC protein (UniProt ID: O83782...

Tracking the within-patient evolution of SARS-CoV-2 is key to understanding how this pandemic virus shapes its genome toward immune evasion and survival. In the present study, by monitoring a long-term COVID-19 immunocompromised patient, we observed the concurrent emergence of mutations potentially associated with immune evasion and/or enhanced transmission, mostly targeting the SARS-CoV-2 key host-interacting protein and antigen.

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia-a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal-using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.

Background: Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) leads to respiratory failure and obstructive alveolar damage, which may be fatal in immunocompromised individuals. COVID19 pandemic has badly affected every part of world, and still situation in world is getting worse with emergence of novel variants. The aim of our study is to explore the genome of SARS-CoV2 followed by in silico reverse vaccinology analysis. This will help to identify the most putative vaccine candidate against the virus in robust manner and enables cost effective development of vaccines compared with traditional strategies. Methods: The genomic sequencing data is retrieved from NCBI (Reference Sequence Number NC_045512.2). The sequences are explored through comparative genomics approaches by GENOMICS to find out the core genome. Comprehensive set of proteins obtained was employed in computational vaccinology approaches for prediction of best possible B and T cell epitopes through ABCpred and IEDB Analysis Resource, respectively. The multi-epitopes were further tested against human toll like receptor and cloned in E. coli plasmid vector in silico.

The phytotherapeutic properties of  Glycyrrhiza glabra (licorice) extract are mainly attributed to glycyrrhizin (GR) and glycyrrhetinic acid (GA). Among their possible pharmacological actions, the ability to act against viruses belonging to different families, including SARS coronavirus, is particularly important. With the COVID-19 emergency and the urgent need for compounds to counteract the pandemic, the antiviral properties of GR and GA, as pure substances or as components of licorice extract, attracted attention in the last year and supported the launch of two clinical trials.In silico docking studies reported that GR and GA may directly interact with the key players in viral internalization and replication such as angiotensin-converting enzyme 2 (ACE2), spike protein, the host transmembrane serine protease 2, and 3-chymotrypsin-like cysteine protease. In vitro data indicated that GR can interfere with virus entry by directly interacting with ACE2 and spike, with a non specific effect on cell and viral membranes. Additional anti-inflammatory and antioxidant effects of GR cannot be excluded. These multiple activities of GR and licorice extract are critically re-assessed in this review, and their possible role against the spread of the SARS-CoV-2 and the features of COVID-19 disease is discussed.

Introduction: SARS-CoV-2 spread rapidly causing a public health crisis worldwide. Currently, emergency vaccines developed against COVID-19 has been used jointly with the adoption of measures to reduce virus transmission are strategies to control the pandemic. However, emergency of new SARS-CoV-2 variants carrying mutations at the spike can become a challenge in vaccine effectiveness and diagnostic detection based only on the spike antigen. The nucleocapsid (N) protein is a 50 kDa protein that plays an important role in replication, transcription and assembly of the viral genome, further to impair the reproductive cycle of the host cell. Also, is the most abundant protein among coronaviruses, highly conserved and particularly immunogenic.

Identification of potential drug-target interaction for approved drugs serves as the basis of repurposing drugs. Studies have shown polypharmacology as common phenomenon. In-silico approaches help in screening large compound libraries at once which could take years in a laboratory. We screened a library of 1050 FDA-approved drugs against spike glycoprotein of SARS-CoV2 in-silico. Anti-cancer drugs have shown good binding affinity which is much better than hydroxychloroquine and arbidol. We have also introduced a hypothesis named “Bump” hypothesis which and be developed further in field of computational biology.

Coronavirus are viruses that can be transmitted to human and animals. Severe acute respiratory syndrome, middle east respiratory syndrome, and Coronavirus disease 2019 are disease can be caused by several subtypes of coronavirus.  The aims of this study were to mapping of the coronavirus circulating in Asia based on sequence of gene spike and membrane protein virus. Totally of 67 coronavirus spike protein and membrane gene sequence were accessed via GenBank® (www.ncbi.nlm.nih.gov/genbank/) matched with the ClustalW Method MEGA-X. The result of the study are 20 groups of coronavirus were found based on spike protein gene sequences and 27 groups of coronavirus were found based on membrane protein gene sequences which were different with the first group of coronavirus found in Wuhan. Therefore, it can be concluded that the coronavirus circulate in several Asian countries had been mutate on gene spike and membrane protein. Keywords: Asia, Coronavirus, MEGA-X, Membrane Protein, Spike Protei

The COVID-19 pandemic has put a tremendous stress on the medical community over the last two years. Managing the infection proved a lot more difficult after several research communities started to recognize the long-term effects of this disease. The cellular receptor for the virus was identified as angiotensin-converting enzyme-2 (ACE2), a molecule responsible for a wide array of processes, broadly variable amongst different organs. Angiotensin (Ang) 1-7 is the product of Ang II, a decaying reaction catalysed by ACE2. The effects observed after altering the level of ACE2 are essentially related to the variation of Ang 1-7. The renin-angiotensin-aldosterone system (RAAS) is comprised of two main branches, with ACE2 representing a crucial component of the protective part of the complex. The ACE2/Ang (1-7) axis is well represented in the testis, heart, brain, kidney, and intestine. Infection with the novel SARS-CoV-2 virus determines downregulation of ACE2 and interrupts the equilibrium between ACE and ACE2 in these organs. In this review, we highlight the link between the local effects of RAAS and the consequences of COVID-19 infection as they arise from observational studies.

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week...

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been declared a pandemic by WHO. The clinical manifestation and disease progression in COVID-19 patients varies from minimal symptoms to severe respiratory issues with multiple organ failure. Understanding the mechanism of SARS-CoV-2 interaction with host cells will provide key insights into the effective molecular targets for the development of novel therapeutics. Recent studies have identified virus-mediated phosphorylation or activation of some major signaling pathways, such as ERK1/2, JNK, p38, PI3K/AKT and NF-κB signaling, that potentially elicit the cytokine storm that serves as a major cause of tissue injuries. Several studies highlight the aggressive inflammatory response particularly 'cytokine storm' in SARS-CoV-2 patients. A depiction of host molecular dynamics triggered by SARS-CoV-2 in the form of a network of signaling molecules will be helpful for COVID-19 research. Therefore, we developed the signaling pathway map of SARS-CoV-2 infection using data mined from the recently published literature. This integrated signaling pathway map of SARS-CoV-2 consists of 326 proteins and 73 reactions. These include information pertaining to 1,629 molecular association events, 30 enzyme catalysis events, 43 activation/inhibition events, and 8,531 gene regulation events. The pathway map is publicly available through WikiPathways: https:// www. wikip athwa ys. org/ index. php/ Pathw ay: WP5115.

Desde el inicio de las inoculaciones de las terapias génicas experimentales llamadas "vacunas Covid", se está observando la presencia de sintomatología multisistémica de diferentes tipos y gravedades. Se reporta el caso de una necrosis del pie tras la vacunación con una dosis. Se plantea la etiología inflamatoria vascular mediada por la interacción de la proteína S (producida por expresión génica) y la unión al receptor ACE2 presente en tejido vascular. La enfermería tiene un papel fundamental en el rastreo de los efectos adversos a corto, medio y largo plazo. Palabras clave: Vacuna Covid. Proteína Espiga. Receptores ACE2. Necrosis. Isquemia. Vasculitis.

Mucormycosis is a group of infections, caused by multiple fungal species, which affect many human organs and is lethal in immunocompromised patients. During the COVID-19 pandemic, the current wave of mucormycosis is a challenge to medical professionals as its effects are multiplied because of the severity of COVID-19 infection. The variant of concern, Omicron, has been linked to fatal mucormycosis infections in the US and Asia. Consequently, current postdiagnostic treatments of mucormycosis have been rendered unsatisfactory. In this hour of need, a preinfection cure is needed that may prevent lethal infections in immunocompromised individuals. This study proposes a potential vaccine construct targeting mucor and rhizopus species responsible for mucormycosis infections, providing immunoprotection to immunocompromised patients. The vaccine construct, with an antigenicity score of 0.75 covering, on average, 92–98% of the world population, was designed using an immunoinformatics approac...

Chicken anemia virus (CAV) causes severe clinical and sub-clinical infection in poultry globally and thus leads to economic losses. The drawbacks of the commercially available vaccines against CAV disease signal the need for a novel, safe, and effective vaccine design. In this study, a multiepitope vaccine (MEV) consisting of T-cell and B-cell epitopes from CAV viral proteins (VP1 and VP2) was computationally constructed with the help of linkers and adjuvant. The 3D model of the MEV construct was refined and validated by different online bioinformatics tools. Molecular docking showed stable interaction of the MEV construct with TLR3, and this was confirmed by Molecular Dynamics Simulation. Codon optimization and in silico cloning of the vaccine in pET-28a (+) vector also showed its potential expression in the E. coli K12 system. The immune simulation also indicated the ability of this vaccine to induce an effective immune response against this virus. Although the vaccine in this stu...

Background: This paper adopted scientific approach to validate the WHO/NCDC safety counseling guidelines to prevent the spread of the SARS-COV 2 coronaviruses in Nigeria in the guidance and counseling perspectives using the sequence characteristics of SARS-COV 2 in Nigeria as validation criterion. Methods: Five hypotheses were used to validate the safety counseling guidelines currently operational globally. Bioinformatics analysis of retrieved RdRP sequences was adopted. Results: All alternate hypotheses were accepted indicating the validity of each of the criterion. Indicators validated included the use of soap (foam) can dissolve the fatty layer of the virus protein coat through regular washing of hands. Heat (high temperature) above 26°C can melt the virus Original Research Article

We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV.  Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences, including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds.

Serratia marcescens is now an important opportunistic pathogen that can cause serious infections in hospitalized or immunocompromised patients. Here, we used extensive bioinformatic analyses based on reverse vaccinology and subtractive proteomics-based approach to predict potential vaccine candidates against S. marcescens. We analyzed the complete proteome sequence of 49 isolate of Serratia marcescens and identified 5 that were conserved proteins, non-homologous from human and gut flora, extracellular or exported to the outer membrane, and antigenic. The identified proteins were used to select 5 CTL, 12 HTL, and 12 BCL epitopes antigenic, non-allergenic, conserved, hydrophilic, and non-toxic. In addition, HTL epitopes were able to induce interferon-gamma immune response. The selected peptides were used to design 4 multi-epitope vaccines constructs (SMV1, SMV2, SMV3 and SMV4) with immune-modulating adjuvants, PADRE sequence, and linkers. Peptide cleavage analysis showed that antigen ...