ABSTRACT
COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV- 2.COVID-19 is now a pandemic, and is not yet fully under control.As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission.The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVII)-19.Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1 ) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2) , the specific receptor of SARS-CoV-2, is introduced in detail.Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV- 2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary.(2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways.With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2) , lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane.(3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type.(4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied.Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment.Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.Copyright © Palaeogeography (Chinese Edition).All right reserved.
ABSTRACT
Monitoring of the proportion of immune individuals and the effectiveness of vaccination in a population involves evaluation of several important parameters, including the level of virus-neutralising antibodies. In order to combat the COVID-19 pandemic, it is essential to develop approaches to detecting SARS-CoV-2 neutralising antibodies by safe, simple and rapid methods that do not require live viruses. To develop a test system for enzyme-linked immunosorbent assay (ELISA) that detects potential neutralising antibodies, it is necessary to obtain a highly purified recombinant receptor-binding domain (RBD) of the spike (S) protein with high avidity for specific antibodies. The aim of the study was to obtain and characterise a SARSCoV-2 S-protein RBD homodimer and a recombinant RBD-expressing cell line, as well as to create an ELISA system for detecting potential neutralising antibodies. Material(s) and Method(s): the genetic construct was designed in silico. To generate a stable producer cell line, the authors transfected CHO-S cells, subjected them to antibiotic pressure, and selected the optimal clone. To isolate monomeric and homodimeric RBD forms, the authors purified the recombinant RBD by chromatographic methods. Further, they analysed the activity of the RBD forms by Western blotting, bio-layer interferometry, and indirect ELISA. The analysis involved monoclonal antibodies GamXRH19, GamP2C5, and h6g3, as well as serum samples from volunteers vaccinated with Gam-COVID-Vac (Sputnik V) and unvaccinated ones. Result(s): the authors produced the CHO-S cell line for stable expression of the recombinant SARS-CoV-2 S-protein RBD. The study demonstrated the recombinant RBD's ability to homodimerise after fed-batch cultivation of the cell line for more than 7 days due to the presence of unpaired cysteines. The purified recombinant RBD yield from culture broth was 30-50 mg/L. Monomeric and homodimeric RBD forms were separated using gel-filtration chromatography and characterised by their ability to interact with specific monoclonal antibodies, as well as with serum samples from vaccinated volunteers. The homodimeric recombinant RBD showed increased avidity for both monoclonal and immune sera antibodies. Conclusion(s): the homodimeric recombinant RBD may be more preferable for the analysis of levels of antibodies to the receptor-binding domain of the SARS-CoV-2 S protein.Copyright © 2023 Authors. All rights reserved.
ABSTRACT
COVID-19, caused by the novel SARS-CoV-2 virus, poses major challenges for global public health. The detection of antibodies in blood serum is one of the important methods for diagnostics of COVID-19 patients. The main aim was to study the dynamics of the appearance of neutralizing antibodies and antibodies to the SARS-CoV-2 proteins in COVID-19 patients sera. Material and methods. The blood sera of four groups of people were studied: "intact" donors (blood sera were collected in 2016-2019);patients with a laboratory-confirmed diagnosis of acute respiratory viral infection;patients with influenza (antibodies to the influenza virus have been identified) and patients with a PCR confirmed diagnosis of COVID-19. Blood sera were analyzed in ELISA with commercial kits for detection of IgG to SARS-CoV-2 (N, S) proteins and total antibodies to RBD of protein S and in neutralization test (NT). Results and discussion. Antibodies to SARS-CoV-2 were not detected in paired blood sera of people from groups 1-3 by ELISA and NT. At the time of hospitalization of patients with COVID-19 in the sera of 12 (19%) patients antibodies to SARS-CoV-2 were absent when they were determined by NT and ELISA. In blood sera taken 4-9 days after hospitalization, neutralizing antibodies and antibodies to at least one viral protein were detected in ELISA. Conclusion. At the time of hospitalization, the overwhelming majority of patients had a humoral immune response to the SARS-CoV-2. In the dynamics of observation, the levels of antibodies to SARS-CoV-2 proteins increased, to a greater extent to RBD.Copyright © 2022 Geotar Media Publishing Group
ABSTRACT
Coronavirus disease 2019 (Covid 19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV 2) and causes lymphopenia, immunosuppression, inefficient T and B cell immunity, cytokine storm, and destructive tissue inflammation. Since COVID 19 is a multi-system disease predominantly affecting the lungs, there is doubt on whether chronic lung diseases place patients at higher risk and SARS CoV2 leads to asthma exacerbation. None of the studies have reported asthma or recurrent wheezing as a comorbidity or risk factor for Covid 19 in children up to now. Notably, further studies are needed to explore the relationship between Covid 19 and asthma to improve clinical practice and decrease morbidity and mortality.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.
ABSTRACT
The coronavirus disease-19 (COVID-19) signs mostly include fever and respiratory symptoms (unusual viral pneumonia by SARS-Coronaviruses 2 or SARS-CoV-2). The Receptor-Binding Domain (RBD) of COVID-19 and SARS-CoV are similar, causing cross-reactivity of anti-SARSCoV antibodies with associated spike protein, exerting promising implications for rapid development of vaccines and therapeutic antibodies against COVID-19. ACE2 is the SARS TMPRSS2 for spike (S) protein receptor for initiation of infection;hence, it is a target for pharmacological intervention. Furthermore, designing novel monoclonal antibodies binding specifically to COVID-19 RBD is essential. A viral S proteins (TMPRSS2) was proposed for clinical use by blocking the viral intake by cell.Copyright © 2020, Health Biotechnology and Biopharma. All rights reserved.
ABSTRACT
Despite the rapid accumulation of facts about the humoral immune response in COVID-19, there are still no evidence-based answers to questions about the factors influencing the level and duration of the detection period of antibodies to SARS-CoV-2 in the blood. Objective(s): To assess the prevalence, clinical and demographic associations of IgG antibodies to RBD of the SARSCoV-2 spike protein at different times after COVID-19. Materials and methods. Residents of the Altai region of Russia, Caucasians aged 20-93 years, who had COVID-19 from May 2020 to February 2021 (n = 314), took part in a onetime observational study. The level of antibodies in the blood was measured by enzyme-linked immunosorbent assay 1-14 months after the onset of the clinical manifestation of CO-VID-19. Results. Anti-RBD IgG antibodies of the SARS-CoV-2 spike protein were detected in 86.9% of the study participants. The dependence of the antibody titer on the duration of the period after COVID-19 was not revealed. The antibody titer was positively correlated with the complication of CO-VID-19 pneumonia and the volume of lung tissue lesions. The presence of pneumonia COVID-19 and the volume of lung tissue lesions are positively associated with age. Age positively correlated with antibody titer regardless of the pneumonia COVID-19 in the anamnesis. Conclusion. IgG antibodies to RBD of the SARS-CoV-2 spike protein are present in most of the COVID-19 patients. The titer of these antibodies in adults depends on age, complications of pneumonia COVID-19, and probably persists up to 14 months after the first symptoms of infection appear.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
ABSTRACT
Motor chronic inflammatory demyelinating polyneuropathy (M-CIDP) is a form of atypical CIDP. This article presents a clinical observation of M-CIDP in a 15-year-old boy, as well as a description of laboratory and instrumental diagnostic data. The boy had a chronic development (> 2 months) of flaccid tetraparesis, predominantly of the proximal muscles of the limbs, without sensory disorders. According to electroneuromyography, there were signs of demyelinating lesions of the proximal parts of the peripheral nerves. There was an increase in the thickness of the nerves of the upper limbs according to ultrasound. In the liquor protein-cell dissociation, as well as in the blood, IgG antibodies to the surface glycoprotein S of the SARS-CoV-2 coronavirus were found. The clinical and neurophysiological picture corresponded to the reliable criteria for CIDP. The therapy with intravenous immunoglobulins had a significant positive effect in the form of an increase in the strength of the limb muscles.Copyright © Russian Neurological Journal. All rights reserved.
ABSTRACT
In November 2020, the Armed Forces of the Russian Federation began mass immunisation of the personnel with Gam-COVID-Vac (Sputnik V), the first Russia vaccine against the new coronavirus infection (COVID-19). Thus, it became necessary to assess post-vaccination antibody levels and the duration and intensity of humoral immunity to COVID-19. The aim of the study was to investigate the immunogenicity and efficacy of Gam-COVID-Vac in military medical staff after vaccination. Material(s) and Method(s): the authors determined the presence of specific antibodies in the serum of individuals immunised with Gam-COVID-Vac (477 volunteers) and COVID-19 convalescents (73 patients), using virus neutralisation (VN), enzyme-linked immunosorbent assay (ELISA) with reagent kits by several manufacturers, and immunoblotting. The results of the study were evaluated using analysis of variance. Result(s): VN detected virus neutralising antibodies in 90.7% of vaccinated subjects;ELISA, in 95.4%. Both VN and ELISA showed lower antibody levels in the vaccinated over 50 years of age. ELISA demonstrated a significantly higher concentration of anti-SARS-CoV-2 spike IgG in the Gam-COVID-Vac group than in the COVID-19 convalescent group. The correlation between antibody detection results by VN and ELISA was the strongest when the authors used their experimental reagent kit for quantitative detection of virus neutralising antibodies by competitive ELISA with the recombinant human ACE2 receptor. Having analysed the time course of neutralising antibody titres, the authors noted a significant, more than two-fold decrease in geometric means of the titres three months after administration of the second vaccine component. Conclusion(s): the subjects vaccinated with Gam-COVID-Vac gain effective humoral immunity to COVID-19. The decrease in titres indicates the need for revaccination in 6 months.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.
ABSTRACT
SARS-CoV-2 is continually evolving with the emergence of new variants with increased viral pathogenicity. The emergence of heavily mutated Omicron (B.1.1.529) with spike protein mutations are known to mediate its higher transmissibility and immune escape that has brought newer challenges for global public health to contain SARS-CoV-2 infection. One has to come up with a therapeutic strategy against the virus so as to effectively contain the infection and spread. Natural phytochemicals are being considered a significant source of bioactive compounds possessing an antiviral therapeutic potential. Being a promising anticancer and chemo-preventive agent, Silybin holds a significant potential to be used as a therapeutic. In the present study, molecular docking of Silybin with Omicron spike protein (7QNW) was carried out. Molecular docking results showed greater stability of Silybin in the active site of the Omicron spike protein with suitable binding mode of interactions. The study reveals that Silybin has the potential to block the host ACE2 receptor-viral spike protein binding;thereby inhibiting the viral entry to human cells. Therefore, Silybin may be further developed as a medication with the ability to effectively combat SARS-CoV-2 Omicron.Copyright © The Author(s) 2023.
ABSTRACT
Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19. Although age is a risk factor for COVID-19, how age affects SARS-CoV-2-specific T cell responses remains unknown. We found that pre-existing T cell responses to specific SARS-CoV-2 proteins, Spike (S) and Nucleoprotein (N), were significantly lower in elderly donors (>70 years old) than in young donors. However, substantial pre-existing T cell responses to the viral membrane (M) protein were detected in both young and elderly donors. In contrast, young and elderly donors exhibited comparable T cell responses to S, N, and M proteins after infection with SARS-CoV-2. These data suggest that although SARS-CoV-2 infection can induce T cell responses specific to various viral antigens regardless of age, diversity of target antigen repertoire for long-lived memory T cells specific for SARS-CoV-2 may decline with age;however, memory T cell responses can be maintained by T cells reactive to specific viral proteins such as M. A better understanding of the role of pre-existing SARS-CoV-2-specific T cells that are less susceptible to age-related loss may contribute to development of more effective vaccines for elderly people.Copyright © 2021
ABSTRACT
As the coronavirus disease 2019 (COVID-19) spread worldwide, variants viruses are constantly emerging. And there has been a growing interest in the study of variant viruses, for the necessity of response to emergence and diffusion of new coronavirus variants. So, we conducted a survey of variant proportions of SARS-CoV-2 on positive samples of confirmed cases by Real-time Polymerase Chain Reaction (Real-time PCR). From December 26, 2021 to April 2, 2022, a total of 819 SARS-CoV-2 variants of concern (VOCs) were identified in COVID-19 positive samples. In the 2nd week of January 2022, detection rate of the Omicron subvariant BA.1 was 58.1%, overtaking Delta variant to become dominant type. However, in the 5th week of March, detection rate of another Omicron subvariant BA.2 was 75.9%, became dominant variant. These results imply that BA.1 was a dominant variant for two months and after that, omicron BA.1 was rapidly replaced by omicron BA.2. This research is valuable because it provided information which is helpful to response diffusion of new variants. Compared to Delta variant, a large number of mutations in the spike gene(S) of Omicron variant were detected. It raises concerns about changes in pathogenicity and transmissibility in new COVID variants. Therefore, we should develop new strategies against emergence and diffusion of SARS-CoV-2 variants throughout monitoring appearance of the new variants, analyzing the characteristics of new things. In this respect, the results of this research are useful because they offered good basic data for appreciating characteristics of new COVID variants by monitoring the emergence of Delta and Omicron variant. Copyright © 2022 Journal of Bacteriology and Virology.
ABSTRACT
Booster vaccine doses are meant to revive the fading immunity created by prior exposure to an immunizing antigen. They stabilize the antibody response ultimately leading to longer and higher protection against pathogens. Immunological studies done for COVID-19 vaccines have documented a steady decrease in antibody levels among vaccinated individuals and evidence of breakthrough infections over a course of time. With an emerging science behind the need for COVID-19 vaccine booster shots, there equally is a contrasting idea regarding its absolute necessity. Copyright © 2021, Kathmandu University. All rights reserved.