Extracellular Vesicle-Based SARS-CoV-2 Vaccine

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 539 - 539

Published: Feb. 24, 2023

Messenger ribonucleic acid (RNA) vaccines are mainly used as SARS-CoV-2 vaccines. Despite several issues concerning storage, stability, effective period, and side effects, viral vector widely for the prevention treatment of various diseases. Recently, vector-encapsulated extracellular vesicles (EVs) have been suggested useful tools, owing to their safety ability escape from neutral antibodies. Herein, we summarize possible cellular mechanisms underlying EV-based

Language: Английский

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Glutathione-related antioxidant defence, DNA damage, and DNA repair in patients suffering from post-COVID conditions

Mutagenesis, Journal Year: 2023, Volume and Issue: 38(4), P. 216 - 226

Published: July 1, 2023

Post-COVID conditions are defined as the continuation of symptoms Coronavirus Disease 2019 (COVID-19) 3 months after initial Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infection, with no other explanation. seen among 30%-60% patients asymptomatic or mild forms COVID-19. The underlying pathophysiological mechanisms post-COVID not known. In SARS-CoV-2 activation immune system leads to increased production reactive oxygen molecules, depleted antioxidant reserve, and finally occurrence oxidative stress. stress conditions, DNA damage increases repair systems impair. this study, glutathione (GSH) level, peroxidase (GPx) activity, 8-hydroxydeoxyguanosine (8-OHdG) basal, induced, post-repair were investigated in individuals suffering from conditions. red blood cells, GSH levels GPx activities measured a spectrophotometric assay commercial kit. Basal, vitro H2O2 (hydrogen peroxide)-induced, (DNA incubation following H2O2-treatment, vitro) determined lymphocytes by comet assay. urinary 8-OHdG using ELISA No significant difference was found between patient control groups for basal H2O2-induced damage. Post-repair be higher group than those group. Urinary level lower compared group, vaccinated individuals. conclusion, formed due response against SARS-COV-2 may impair mechanisms. Defective an pathological mechanism

Language: Английский

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Mapping the Lipid Signatures in COVID-19 Infection: Diagnostic and Therapeutic Solutions

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(21), P. 14411 - 14433

Published: Oct. 30, 2023

The COVID-19 pandemic ignited research centered around the identification of robust biomarkers and therapeutic targets. SARS-CoV-2, virus responsible, hijacks metabolic machinery host cells. It relies on lipids lipoproteins cells for entry, trafficking, immune evasion, viral replication, exocytosis. infection causes cell lipid remodelling. Targeting lipid-based processes is thus a promising strategy countering COVID-19. Here, we review role in different steps SARS-CoV-2 pathogenesis identify lipid-centric targetable avenues. We discuss lipidome changes infected patients their relevance as potential clinical diagnostic or prognostic biomarkers. summarize emerging direct indirect approaches targeting using lipid-inspired approaches. Given that protein-targeted therapies may become less effective due to mutations variants, interventions provide additional perhaps better means combating this future pandemics.

Language: Английский

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Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 13, 2023

Nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection replication. Thus, inhibiting XPO1-mediated nuclear export with selective inhibitors activates multiple antiviral anti-inflammatory pathways. The inhibitor, Selinexor, is an FDA-approved anticancer drug predicted have function against many viruses, including SARS-CoV-2. Unexpectedly, we observed that pretreatment cultured human cells Selinexor actually enhanced protein expression replication coronaviruses, Knockdown cellular significantly the coronaviruses cells. We further demonstrate treatment reduced formation unique cytoplasmic granules include RNA helicase DHX9 virus-infected These results, for first time, show anti-cancer enhances vitro thus should be explored vivo potential impact on dual use therapy.

Language: Английский

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NucEnvDB: A Database of Nuclear Envelope Proteins and Their Interactions

Membranes, Journal Year: 2023, Volume and Issue: 13(1), P. 62 - 62

Published: Jan. 3, 2023

The nuclear envelope (NE) is a double-membrane system surrounding the nucleus of eukaryotic cells. A large number proteins are localized in NE, performing wide variety functions, from bidirectional exchange molecules between cytoplasm and to chromatin tethering, genome organization, regulation signaling cascades, many others. Despite its importance, several aspects including protein-protein interactions, remain understudied. In this work, we present NucEnvDB, publicly available database NE their interactions. Each entry contains useful annotation description position interactions with other proteins, cross-references major biological repositories. addition, provides users visualization analysis tools, ability construct visualize interaction networks perform functional enrichment for clusters partners. capabilities NucEnvDB tools showcased by two informative case studies, exploring Hutchinson-Gilford progeria during SARS-CoV-2 infection at level envelope.

Language: Английский

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COVID-19: Perspectives on innate immune evasion

Progress in molecular biology and translational science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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Understanding the Molecular Actions of Spike Glycoprotein in SARS-CoV-2 and Issues of a Novel Therapeutic Strategy for the COVID-19 Vaccine

BioMedInformatics, Journal Year: 2024, Volume and Issue: 4(2), P. 1531 - 1555

Published: June 9, 2024

In vaccine development, many use the spike protein (S protein), which has multiple “spike-like” structures protruding from spherical structure of coronavirus, as an antigen. However, there are concerns about its effectiveness and toxicity. When S is used in a vaccine, ability to attack viruses may be weak, eliciting immunity will only last for short period time. Moreover, it cause “antibody-dependent immune enhancement”, can enhance infections. addition, three-dimensional (3D) epitopes essential functional analysis structure-based design. Additionally, during viral infection, large amounts extracellular vesicles (EVs) secreted infected cells, function communication network between cells coordinate response infection. Under conditions where SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) molecular vaccination produces overwhelming glycoprotein, significant proportion overproduced intracellular glycoprotein transported via EVs. Therefore, important understand infection mechanisms SARA-CoV-2 EV-dependent EV-independent uptake into model processes based on 3D structural features at interaction sites.

Language: Английский

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Exploring the Replication and Pathogenic Characteristics of Alpha, Delta, and Omicron Variants of SARS-CoV-2

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12641 - 12641

Published: Nov. 25, 2024

The variants of concern (VOCs) SARS-CoV-2 have exhibited different phenotypic characteristics in clinical settings which are yet to be fully explored. This study aimed characterize the viral replication features major VOCs and their association with pathogenicity. Alpha, Delta, Omicron isolated from COVID-19 patients Japan were propagated VeroE6/TMPRSS2 cells. pathological evaluated by laser electron microscopy at time points. results revealed that Delta variant dominantly infected cells formed increased syncytia compared Alpha variants. Relatively large numbers virions immunoreactivities N-protein detected endoplasmic reticulum intracellular vesicles Delta-infected Interestingly, nucleus cells, while such properties not observed case In addition, early nuclear membrane damage followed severe cellular was prominent A unique mutation (G215C) is thought associated cell damage. conclusion, this highlights distinct replicative pathogenic variants, shedding light on potential mechanisms underlying its

Language: Английский

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Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus

BMC Genomic Data, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 17, 2024

Abstract Objectives SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it unique among sarbecoviruses but frequently found betacoronaviruses. Recent evidence suggests that this includes two additional functional motifs: pat7 nuclear localization signal flanking O -glycosites. However, systematic genus subgenus analysis protein sequences bearing polyfunctional sequence domain has been missing. Data description Here we report comprehensive data to demonstrate proteins Betacoronavirus outside clade fully analogous was in only one other virus: artificial MERS infectious clone MERS-MA30, described already 2017, which rationally selected from serial passage genetically humanized mice. As evolutionarily closest betacoronaviruses lack all its three motifs, these extend—beyond natural evolution zoonosis—the current view on pre-pandemic origins by presenting MERS-MA30 as precise molecular blueprint for SARS-CoV-2.

Language: Английский

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Expression, purification and immunogenicity analyses of receptor binding domain protein of severe acute respiratory syndrome coronavirus 2 from delta variant.

PubMed, Journal Year: 2024, Volume and Issue: 15(12), P. 657 - 663

Published: Jan. 1, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. The receptor binding domain (RBD), located at spike protein of SARS-CoV-2, contains most neutralizing epitopes during viral infection and an ideal antigen vaccine development. In this study, bioinformatic analysis amino acid sequence data SARS-CoV-2 RBD better understanding molecular characteristics was performed. gene inserted into pET-28a vector, efficiently expressed in E. coli system. Then, recombinant proteins (RBD monomer dimer protein) were purified as animal immunization. Furthermore, results showed that had adequate immunogenicity to stimulate specific antibodies against corresponding immunized mice. Taken together, study revealed a high immuno-genicity. This might have implications future development detection.

Language: Английский

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