Functional and Structural Characterization of SARS-Cov-2 Spike Protein: An In Silico Study

BACKGROUND፡ Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global outbreak of coronavirus disease 2019 (Covid-19), which has been considered as a pandemic by WHO. SARS-CoV-2 encodes four major structural proteins, among which spike protein has always been a main target for new vaccine studies. This in silico study aimed to investigate some physicochemical, functional, immunological, and structural features of spike protein using several bioinformatics tools.METHOD: We retrieved all SARS-CoV-2 spike protein sequences from different countries registered in NCBI GenBank. CLC Sequence Viewer was employed to translate and align the sequences, and several programs were utilized to predict B-cell epitopes. Modification sites such as phosphorylation, glycosylation, and disulfide bonds were defined. Secondary and tertiary structures of all sequences were further computed.RESULTS: Some mutations were determined, where only one (D614G) had a high prevalence. The mutations did not impact the B-cell and physicochemical properties of the spike protein. Seven disulfide bonds were specified and also predicted in several N-link glycosylation and phosphorylation sites. The results also indicated that spike protein is a non-allergen.CONCLUSION: In summary, our findings provided a deep understanding of spike protein, which can be valuable for future studies on SARS CoV-2 infections and design of new vaccines

The Effectiveness of the Anteroom (Vestibule) Area on Hospital Infection Control and Health Staff Safety: A Systematic Review

The emergence of SARS-CoV2 in 2019 showed again that the world's healthcare system is not fully equipped and well-designed for preventing the transmission of nosocomial respiratory infections. One of the great tools for preventing the spread of infectious organisms in hospitals is the anteroom. Several articles have investigated the role of the anteroom in disease control but the lack of a comprehensive study in this field prompted us to provide more in-depth information to fill this gap. Also, this study aimed to assess the necessity to construct an anteroom area for hospital staff members at the entrance of each ward of the hospital, and specify the equipment and facilities which make the anteroom more efficient. Articles were identified through searches of Scopus, Web of Sciences, PubMed, and Embase for studies published in English until May 2020 reporting data on the effect of the anteroom (vestibule) area in controlling hospital infections. Data from eligible articles were extracted and presented according to PRISMA's evidence-based data evaluation search strategy. Also, details around the review aims and methods were registered with the PROSPERO. From the database, 209 articles were identified, of which 25 studies met the study criteria. Most studies demonstrated that an anteroom significantly enhances practical system efficiency. The results showed that the equipment such as ventilation system, high-efficiency particulate absorption filter, hand dispensers, alcohol-based disinfection, sink, mirror, transparent panel, UVC disinfection, and zone for PPE change, and parameters like temperature, door type, pressure, and size of the anteroom are factors that are effective on the safety of the hospital environment. Studies demonstrated that providing an anteroom for changing clothing and storing equipment may be useful in reducing the transmission of airborne infections in hospitals. Since the transmission route of SARS-CoV2 is common with other respiratory infectious agents, it can be concluded that a well-designed anteroom could potentially decrease the risk of SARS-CoV2 transmission during hospitalization as well.publishedVersio

Alzheimer’s Disease and Microorganisms: The Non-coding RNAs Crosstalk

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in response to microbial infections, acts as a defense mechanism for the brain but can inadvertently lead to unexpected neuropathological perturbations, ultimately contributing to NDs. Given the ongoing uncertainty surrounding the genetic factors underpinning ND, comprehensive investigations into environmental factors, particularly the microbiome and viral agents, are imperative. Recent advances in neuroscientific research have unveiled the pivotal role of non-coding RNAs (ncRNAs) in orchestrating various pathways integral to neurodegenerative pathologies. While the upstream regulators governing the pathological manifestations of microorganisms remain elusive, an in-depth exploration of the nuanced role of ncRNAs holds promise for the development of prospective therapeutic interventions. This review aims to elucidate the pivotal role of ncRNAs as master modulators in the realm of neurodegenerative conditions, with a specific focus on Alzheimer’s disease

Targeting CD47 as a therapeutic strategy: A common bridge in the therapy of COVID-19-related cancers

Macrophages are essential mediators of innate immunity. Non-self-cells resist phagocytosis through the expression of the checkpoint molecule CD47. CD47, as the integrin-associated protein, is overexpressed on tumor and SARS-CoV-2-infected cells as a potential surface biomarker for immune surveillance evasion. CD47-signal-regulating protein alpha (SIRPα) interaction is a promising innate immunotarget. Previous findings based on monoclonal antibodies (mAbs) or fusion proteins that block CD47 or SIRPα have been developed in cancer research. While CD47 efficacy in infectious diseases, especially severe COVID-19 studies, is lacking, focus on macrophage-mediated immunotherapy that increases “eat me” signals in combination therapy with mAbs is optimistic. This integrin-related protein can be as a potential target to therapy for COVID-19. Here, we concentrate on the role of the CD47 signaling pathway as a novel therapeutic strategy for COVID-19-associated cancer treatment

Design, cloning and expression assay of oipA gene in a bicistronic vector harboring mice IL-18 gene: potential implications for Helicobacter pylori vaccine investigations

Introduction: Helicobacter pylori (H. pylori) infection has remained as a global health problem. Animal studies demonstrated the role of H. pylori oipA gene in the development of gastric cancer. The aim of this study was the cloning and expression of Helicobacter pylori oipA gene in a bicistronic vector harboring mice IL-18 gene. Materials and methods: The target gene encoding oipA was amplified from a codon-optimized clone by PCR, and then double-digested by restriction enzymes. The pIRES-Igk/mIL18/Fc plasmid was simultaneously digested by BstXI/NotI enzymes to elicit the eGFP segment. PCR product of oipA was inserted into pIRES-Igk/mIL18/Fc plasmid using T4 ligase. Transformation into DH5α strain was done. Cloning was confirmed by PCR, enzymatic digestion and sequencing. Expression of the oipA and IL-18 mRNA was assessed by means of TaqMan Real-time PCR. Results: Electrophoresis of PCR product, enzymatic digestion and sequencing showed that the H. pylori oipA gene was successfully cloned into pIRES-Igk/mIL18/Fc to generate mIL-18-pIRES2-oipA plasmid. The results of Real-time PCR confirmed the successful expression of both oipA and IL-18 in mouse macrophage cell line. Conclusion: Considering the role of oipA in pathogenesis of H. pylori and potent activity of IL-18 as a molecular adjuvant, the results of the present study showed that the expression of codon-optimized oipA gene in bicistronic vector including mouse IL-18 is successful. So, it could be considered as an appropriate genetic vaccine candidate for H. pylori in future investigations

The Effectiveness of the Anteroom (Vestibule) Area on Hospital Infection Control and Health Staff Safety: A Systematic Review

The emergence of SARS-CoV2 in 2019 showed again that the world's healthcare system is not fully equipped and well-designed for preventing the transmission of nosocomial respiratory infections. One of the great tools for preventing the spread of infectious organisms in hospitals is the anteroom. Several articles have investigated the role of the anteroom in disease control but the lack of a comprehensive study in this field prompted us to provide more in-depth information to fill this gap. Also, this study aimed to assess the necessity to construct an anteroom area for hospital staff members at the entrance of each ward of the hospital, and specify the equipment and facilities which make the anteroom more efficient. Articles were identified through searches of Scopus, Web of Sciences, PubMed, and Embase for studies published in English until May 2020 reporting data on the effect of the anteroom (vestibule) area in controlling hospital infections. Data from eligible articles were extracted and presented according to PRISMA's evidence-based data evaluation search strategy. Also, details around the review aims and methods were registered with the PROSPERO. From the database, 209 articles were identified, of which 25 studies met the study criteria. Most studies demonstrated that an anteroom significantly enhances practical system efficiency. The results showed that the equipment such as ventilation system, high-efficiency particulate absorption filter, hand dispensers, alcohol-based disinfection, sink, mirror, transparent panel, UVC disinfection, and zone for PPE change, and parameters like temperature, door type, pressure, and size of the anteroom are factors that are effective on the safety of the hospital environment. Studies demonstrated that providing an anteroom for changing clothing and storing equipment may be useful in reducing the transmission of airborne infections in hospitals. Since the transmission route of SARS-CoV2 is common with other respiratory infectious agents, it can be concluded that a well-designed anteroom could potentially decrease the risk of SARS-CoV2 transmission during hospitalization as well

Cationic influenza virosomes as an adjuvanted delivery system for CTL induction by DNA vaccination

DNA vaccines have emerged as an attractive approach to induce CTL responses against cancer and infectious agents in recent years. Although CTL induction by DNA vaccination would be a valuable strategy for controlling viral infections, increasing the potency of DNA vaccines is mandatory before DNA vaccines can make it to the clinic. In this study, we developed and characterized a new and safe adjuvanted delivery system for DNA vaccination using cationic influenza virosomes (CIV). CIV were produced by reconstitution of detergent-solubilized influenza virus membranes in the presence of cationic lipids. Plasmid DNA (pDNA) mixed with these virosomes was efficiently transfected into cells of a mouse macrophage cell line (RAW-Blue cells). Moreover, the cells were effectively activated as demonstrated by production of an NF kappa B/AP-1-inducible reporter enzyme. Following three intradermal immunizations, CIV-delivered epitope-encoding pDNA induced equal numbers of IFN gamma- and granzyme B-producing T cells than a 10-fold higher dose of naked pDNA. Virosomes without cationic lipids also improved induction of cellular immunity by pDNA but to a significantly lower extent than CIV. These findings suggest that pDNA-CIV complexes could be an efficacious delivery system suitable for CTL induction by DNA vaccination. (C) 2012 Elsevier B.V. All rights reserved