The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry.

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.

Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro.

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHOD(S): The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULT(S): Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 mug/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 mug/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 mumol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 mumol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION(S): Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

Production and characterisation of a SARSCoV-2 S-protein RBD homodimer with increased avidity for specific antibodies.

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.

Determination of antibodies to SARS-CoV-2 in patients with coronavirus infection

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

Childhood asthma and Covid 19

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.

Multiplex measurements of the impacts of ACE2 sequence and cell surface abundance during SARS-like coronavirus entry

SARS-like coronaviruses, including SARS-CoV and SARS-CoV-2, encode spike proteins that bind human ACE2 protein on the cell surface to enter target cells and cause infection. The efficiency of virus entry depends on ACE2 sequence and expression levels in target cells. A small fraction of humans encodes variants of ACE2, thus altering the biochemical properties at the protein interaction interface. All humans possess cells with vastly differing amounts of ACE2 on the cell surface, ranging from cell types with high expression in the gut and lungs to lower expression in the liver and pancreas. Mastering our understanding of spike-ACE2 interaction and infection requires experiments precisely perturbing both variables. Thus, we developed a synthetic cell engineering approach compatible with high throughput assays for pseudo-typed virus infection. Our assay system is capable of assessing both variables individually and in combination. We adapted an engineered HEK293T DNA recombinase landing pad cell line capable of expressing transgenic ACE2 sequences at highly precise levels. Infection with lentiviruses pseudotyped with the spikes of SARS-like coronaviruses revealed that high ACE2 abundance could mask the effects of impaired binding thereby making it challenging to know the role of affinity altering mutations during infection. We limited the ACE2 abundance on the cell surface by expressing transgenic ACE2 behind a suboptimal Kozak sequence, thereby altering its protein translation rate. This allowed us to understand how ACE2 sequence could impact its interaction with coronavirus spike proteins as two human ACE2 variants at the binding interface, K31D and D355N, exhibited reduced infection. Our experiments suggested that we need to better understand how ACE2 expression determines the susceptibility of cells for SARS-like coronavirus binding and infection. We thus created an ACE2 Kozak library consisting of ~4,096 Kozak variants, each conferring a different ACE2 protein translation rate thus resulting in a range of ACE2 steady-state abundances. Combining fluorescence-activated cell sorting and high-throughput DNA sequencing (FACS-seq) revealed the library to span two orders of magnitude of ACE2 abundance. Challenging this library of cells with spike pseudotyped lentiviruses revealed how ACE2 abundance correlated with infection rate. The library-based experiments yielded a dynamic range wider than traditional single sample infection assay, likely more representative of infection dynamics in vivo. Now that we have characterized the impacts of ACE2 abundance on infectivity in engineered cells, our next goal is to expand the comparison to physiologically relevant cells with endogenously expressed proteins. Modulating protein abundance levels will be key to creating maximally informative functional assays for any protein in cell-based assays, and we have laid the groundwork for being able to simultaneously test the impacts of protein abundance and sequence in combination for proteins involved in diverse cellular processes. This research was supported by a National Institute of Health (NIH) grant GM142886 (KAM).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Visualization and functional annotation of coronavirus spike protein glycoshields

Spike proteins of coronaviruses are highly glycosylated and responsible for host recognition and viral entry. The glycans provide a camouflaging shield to help coronaviruses evade host immunity and, in some cases, modulate functional domain structures and dynamics pertinent to host recognition. However, the glycans are chemically and conformationally heterogeneous, making it challenging to determine the chemical compositions and conformations quantitatively. Combining cryo-electron microscopy, mass spectrometry, and molecular modeling, we systematically characterize a panel of spike protein variants of human and animal coronaviruses, including those of the variants of concern of SARS-CoV-2. We have established a robust workflow to quantify the heterogeneity of individual N-glycans by mass spectrometry. We also demonstrated the ability to visualize long glycan structures directly in regions where the dynamics are restricted. In places where the N-glycans are too dynamic, their structural information is generally lost after extended cryo-EM data processing that aims to achieve high resolution. To address this issue, we developed a computational tool called GlycoSHIELD to generate ensembles of glycan conformers to recapitulate the fuzzy structures that are in quantitative agreement with the experimental cryo-EM data. The ability to generate fully glycosylated spike protein models enables the prediction of hitherto unknown receptor and antibody binding sites. This work was supported by Academia Sinica intramural fund, an Academia Sinica Career Development Award, Academia Sinica to STDH (AS-CDA-109- L08), an Infectious Disease Research Supporting Grant to STDH (AS-IDR- 110-08), and the Ministry of Science and Technology (MOST), Taiwan (MOST 109-3114-Y-001-001, MOST 110-2113-M-001- 050-MY3 and MOST 110-2311-B-001-013-MY3) to STDH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Asafetida (Ferula asafoetida) and its Potential Risks on Respiratory Disorders

Ferula asafoetida is an endemic species in Iran and is rich in oleo-gum resin with high economic value in the world. One important application of F. assafoetida is its traditional use for the management of respiratory ailments. The aim of this review was to collect papers dealing with F. asafoetida oleo-gum resin in respiratory tract's diseases in modern medicine. For preparing the manuscript the scientific databases (Google scholar, PubMed, Springer, Science Direct, Magiran), books, thesis, etc. were searched using the keywords of "Ferula asafoetida", "Ferula scorodesma", "Scorodesma foetida", "Northex asafoetida" plus "respiratory tract", "respiratory disorder" "infection", "cough", "trachea", "traditional medicine" up to Feb 2022 and the collected data were sum-marized, analyzed, and discussed. The results of the investigation confirmed the traditional belief on the efficacy of Ferula asafoetida in the treatment of respiratory viral infection (Coronavirus, influ-enza), cigarette smoking, asthma, cough and cancer, but most studies were limited to in vitro. There was only one registered randomized, blinded, placebo controlled clinical trial for 300 mg F. asafoet-ida aqueous extract capsules (three times a day for 14 days) on 40 patients with COVID-19 without any published results. Although, the studies implied the efficacy of F. asafoetida in the treatment of respiratory treatments, but design large clinical studies for evaluating its efficacy and safety is essential in future investigations.Copyright © 2023 Bentham Science Publishers.

Novel coronavirus disease-19:An overviwe of pathogenesis, health influences and measures

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.

Curcumin from Curcuma longa L. as Dual Inhibitors Against Indonesian SARS-CoV-2 Isolates: A Molecular Docking Study

COVID-19 has become a global pandemic since 2020. The search for promising drugs based on the abundant herbal ingredients in Indonesia is one of the breakthroughs. Curcumin is a chemical compound with various potentials such as antioxidant, anti-inflammatory and antiviral. We conducted a molecular docking analysis to determine the potential of curcumin against SARS-CoV-2 non-structural and structural proteins, such as the main protease and spike protein. This study used the compound of curcumin (PubChem CID: 969516) from Curcuma longa L. or turmeric and two Indonesian SARS-CoV-2 isolates that have been deposited in the GISAID database (hCoV-19/Indonesia/JI-PNF-217315/2021 - EPI_ ISL_12777089 or lineage B.1.617.2 and hCoV-19/Indonesia/JI-PNF-211373/2021 - EPI_ISL_6425649 or lineage B.1.470). In addition, we used molnupiravir (PubChem CID: 145996610) as a drug control. We performed molecular docking analysis with PyRx software 0.9.9 (academic license) and visualization of molecular docking results with PyMOL software 2.5.4 (academic license). The results of this study found that curcumin had good potential against main protease and spike protein compared to the drug (control). In summary, we suggested that curcumin is a potential drug candidate against SARS-CoV-2. However, there is a need for future wet laboratory-based pre-clinical research such as in vitro and in vivo.Copyright © 2023 Phcogj.Com.

Assessment of specific T-cell immunity in patients who have been ill and vaccinated against COVID-19.

Introduction. In the context of a pandemic of a new coronavirus infection (COVID-19), research on the peculiarities of the formation of an immune response to SARS-CoV-2 in patients who have been ill and vaccinated is of particular relevance. However, most studies are currently devoted to evaluating only the humoral link of immunity, and its cellular component remains insufficiently studied. The aim of the study was to evaluate the features of the formation and changes of the T-cell link of immunity in patients with a new coronavirus infection and vaccinated against this disease. Materials and methods. The study was performed on the basis of the clinical and diagnostic laboratory of the European Medical Center "UMMC-Health "LLC. Specific T-cell immunity was evaluated using ELISPOT technology. In the course of the study, 72 blood samples of employees of medical organizations were analyzed, including 26 from those who had a new coronavirus infection, 23 from persons who were intact according to COVID-19 before vaccination and 23 from the same employees after vaccination (<<Gam-Covid-Vac>>). In addition, each of the study participants was examined to determine specific class G antibodies (IgG) by solid-phase enzyme immunoassay using SARS-CoV-2-IgG-ELISA-BEST test systems (manufactured by VECTOR-BEST JSC). Results and discussion. In the group of patients (26 people), T-lymphocytes capable of specifically reacting to SARSCoV-2 antigens were detected in 100% of cases, even in individuals with IgG elimination. It should be noted that the response was more pronounced when meeting with M-and N-pepdids, compared with S-protein. 22 out of 23 COVID-19 intact individuals had no T-cell immunity to coronavirus infection before vaccination, but one employee had a response to 3 proteins-M, N, S, which indicates that he had previously encountered the SARS-CoV-2 virus. After vaccination with the drug "Gam-Covid-Vac", 22 (95.6%) employees revealed a T-cell response, while 21-only to S-protein, and an employee with a previously detected immune response-after vaccination, the response to M -, N-proteins remained almost at the same level, and the cellular response to S-peptide doubled. Conclusion. Thus, based on the results of the study, important materials were obtained on the peculiarities of the formation of a specific T-cell immune response to a new coronavirus infection. The obtained data provide a broader understanding of the immune response in new coronavirus infection in patients who have been ill and vaccinated and can be used in the future when planning preventive and anti-epidemic measures.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Endogenous antibody response to SARS-CoV-2 in patients who received monoclonal antibodies against COVID-19: A systematic review

Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.Copyright © 2022

The landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic mutations

Background: This article is aimed to provide an updated landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic mutations emerged since its first identification and sequencing. Method(s): We downloaded and analyzed all mutations within the SARS-CoV-2 RNA genome submitted up to February 8, 2022 to the website of the National Center for Biotechnology Information (NCBI), which contains all variants in Sequence Read Archive (SRA) records compared to the prototype SARS-CoV-2 reference sequence NC_045512.2. Result(s): Our search identified 26,005 different mutations. The largest number of mutations was located within the gene encoding for the Nsp3 protein (20.7%), followed by the gene encoding for the spike protein (14.6%). Overall, 17,948/26,005 (69.0%) of these mutations interested single nucleotide positions, thus spanning over ~62% of the entire SARS-CoV-2 genome. Of all mutations, 61.5% were non-synonymous, whilst 17.4% of those in the gene encoding for the spike protein involved the sequence of the receptor binding domain, 59.2% of which were non-synonymous. When the number of mutations was expressed as ratio to the gene size, the highest ratio was found in the sequence encoding for ORF7a (ratio, 2.25), followed by ORF7b (ratio, 1.85), ORF8 (ratio, 1.60) and ORF3a (ratio, 1.48). The gene encoding for RNA-dependent RNA polymerase accounted for only 0.1% of all mutations, with considerably low ratio with the gene size (i.e., ratio, 0.01). Conclusion(s): The results of our analysis demonstrate that SARS-CoV-2 has enormously mutated since its first sequence has been identified over 2 years ago.Copyright © 2022 AME Publishing Company. All rights reserved.

Antibodies to the receptor-binding domain of the SARS-Cov-2 spike protein: association with age, pneumonia, duration of the period after COVID-19.

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.

MOTOR CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN A CHILD.

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.

Immunogenicity evaluation of Gam-COVID-Vac (Sputnik V).

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.

Computational Docking Study of the Phytochemical Constituent, Silybin (Silybum marianum) against SARS-CoV-2 Omicron Variant Spike Glycoprotein: An In-silico Approach

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.