Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells

Cells, Год журнала: 2024, Номер 13(5), С. 369 - 369

Опубликована: Фев. 21, 2024

A large portion of the heterogeneity in coronavirus disease 2019 (COVID-19) susceptibility and severity illness (SOI) remains poorly understood. Recent evidence suggests that SARS-CoV-2 infection-associated damage to alveolar epithelial type 2 cells (AT2s) distal lung may directly contribute poor prognosis COVID-19 patients. Our vitro modeling infection induced pluripotent stem cell (iPSC)-derived AT2s from 10 different individuals showed interindividual variability postinfection cellular viral load. To understand underlying mechanism AT2's capacity regulate load, a genome-wide differential gene expression analysis between mock infection-challenged was performed. The 1393 genes, which were significantly (one-way ANOVA FDR-corrected

Язык: Английский

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Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses

Vaccines, Год журнала: 2022, Номер 10(11), С. 1805 - 1805

Опубликована: Окт. 26, 2022

The current century has witnessed infections of pandemic proportions caused by Coronaviruses (CoV) including severe acute respiratory syndrome-related CoV (SARS-CoV), Middle East (MERS-CoV) and the recently identified SARS-CoV2. Significantly, SARS-CoV2 outbreak, declared a in early 2020, wreaked devastation imposed intense pressure on medical establishments world-wide short time period spreading at rapid pace, resulting high morbidity mortality. Therefore, there is compelling need to combat contain infections. review addresses unique features molecular virology major that may be tractable towards antiviral targeting design novel preventative therapeutic intervention strategies. Plant-derived vaccines, particular oral afford safer, effectual low-cost avenues develop antivirals fast response requiring minimal infrastructure trained personnel for vaccine administration developing countries. This article discusses recent developments generation plant-based therapeutic/drug molecules, monoclonal antibodies phytochemicals preclude SARS-CoV, MERS-CoV SARS-CoV-2 viruses. Efficacious plant-derived could contribute significantly combating emerging re-emerging pathogenic help stem tide any future pandemics.

Язык: Английский

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Evaluation of the association between clinical parameters and ADAM33 and ORMDL3 asthma gene single-nucleotide polymorphisms with the severity of COVID-19

International Immunopharmacology, Год журнала: 2023, Номер 123, С. 110707 - 110707

Опубликована: Июль 25, 2023

Язык: Английский

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Targeting iRhom2/ADAM17 attenuates COVID-19-induced cytokine release from cultured lung epithelial cells

Biochemistry and Biophysics Reports, Год журнала: 2024, Номер 39, С. 101811 - 101811

Опубликована: Авг. 20, 2024

The COVID-19 pandemic, caused by SARS-CoV-2, continues to pose a significant global health challenge, with acute respiratory distress syndrome (ARDS) being major cause of mortality. Excessive cytokine release (cytokine storm) has been causally related COVID-19-associated ARDS. While TNF-α inhibitors have shown potential in reducing inflammation, their broad effects on signaling, including both pro- and anti-inflammatory pathways, present challenges side clinical use. Therefore, more precise therapeutic targets are urgently needed. ADAM17 is key enzyme driving release, but its presence complicates direct inhibition. Targeting iRhom2, regulator specific immune cells that controls ADAM17's activity, offers focused effective approach release. In this study, we hypothesized targeted inhibition ADAM-17/iRhom2 attenuates COVID-19-induced cultured lung epithelial cells. Human primary bronchial/tracheal challenged pseudo-viral particles resulted elevated which was attenuated following siRNA-mediated silencing iRhom2. pathway may thus represent strategy overcome the • Mortality patients linked proinflammatory cytokines. metalloprotease causes cleavage Blockade via iRhom2 pseudo-particle-induced

Язык: Английский

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Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms

Frontiers in Molecular Medicine, Год журнала: 2023, Номер 2

Опубликована: Янв. 4, 2023

Infection with SARS-CoV-2 coronavirus causes systemic, multi-faceted COVID-19 disease. However, knowledge connecting its intricate clinical manifestations molecular mechanisms remains fragmented. Deciphering the basis of at whole-patient level is paramount to development effective therapeutic approaches. With this goal in mind, we followed an iterative, expert-driven process compile data published prior and during early stages pandemic into a comprehensive model. Recent updates model have also validated multiple earlier predictions, suggesting importance such frameworks hypothesis generation testing. Overall, our findings suggest that perturbs several specific mechanisms, unleashing pathogenesis spectrum, ranging from “a perfect storm” triggered by acute hyper-inflammation, accelerated aging protracted “long COVID-19” syndromes. In work, shortly report on these share community via 1) synopsis key evidence associating symptoms plausible details presented within 2) accompanying “COVID-19 Explorer” webserver, developed specifically for purpose (found https://covid19.molecularhealth.com ). We anticipate will continue facilitate clinico-molecular insights across organ systems together testing potential repurposing drug candidates, new pharmacological targets clinically relevant biomarkers. Our work suggests whole patient models human disease can potentially expedite strategies support evidence-driven decision making.

Язык: Английский

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Do Messenger RNA Vaccines Induce Pathological Syncytia?

International Journal of Pathology and Clinical Research, Год журнала: 2022, Номер 8(2)

Опубликована: Ноя. 11, 2022

subcellular structures [13].The development of such therapeutics is anticipated to redefine clinical pathways, including for non-communicable diseases.However, are these therapies ready worldwide application in their present molecular form?The question has been asked before, often relation the potential toxicity lipid formulations used past, especially as part delivering cancer [14,15].However, following sections, we take a closer look at novel perspective, namely mRNA vaccines' structure and composition unintended biological consequences derived from pathological cell-cell fusion. Messenger RNA Vaccines, an OverviewTo elicit formation neutralizing antibodies, exogenously administered must avoid two key obstacles: Hydrolysis by extracellular RNAases recognition cytosolic innate immune sensors, toll-like receptors (TLRs) retinoic acidinducible gene I (RIG-I) protein [16,17].The former accomplished hiding nucleic acid backbone into LNPs, while latter attaching nucleobases, N1-methylpseudouridine (m1Ψ) [18,19] (Figure 1).The coding region flanked untranslated regions (UTRs) followed polyadenylated (polyA) tail 3' cap 5' ReView ARtiCle

Язык: Английский

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Updates on Inflammatory Molecular Pathways Mediated by ADAM17 in Autoimmunity

Cells, Год журнала: 2024, Номер 13(24), С. 2092 - 2092

Опубликована: Дек. 18, 2024

ADAM17 is a member of the disintegrin and metalloproteinase (ADAM) family transmembrane proteases with immunoregulatory activity in multiple signaling pathways. The functional involved shedding ectodomain characterizing many substrates belonging to growth factors, cytokines, receptors, adhesion molecules. ADAM17-dependent pathways are known be crucial tumor development progression modulation pathological physiological processes. In last decade, was considered driver several autoimmune pathologies, numerous substrate-mediated signal transduction were identified. However, discoveries made date have led researchers try clarify mechanisms which identify any molecular gaps between different transductional cascades. this review, we summarize most recent updates on regulatory activities ADAM17, focusing reported data field autoimmunity.

Язык: Английский

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Comparison of treatment among pulmonary tuberculosis patients with and without Covid- 19 and the impact of type 2 DM

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Июнь 15, 2023

Abstract Background The impact of the coronavirus disease 2019 (COVID-19) pandemic on tuberculosis (TB) was great enough for COVID-19 to replace TB as leading cause death worldwide. WHO Global Tuberculosis Report 2020 stated that number cases reported 845,000. caused a decline in detection cases, and attention Indonesian government became more focused making top priority prevention control measures so were neglected. Methods This study used cross-sectional. research subjects recruited using consecutive sampling technique. variable this comparison between pulmonary with confirmed without total sampling. Bivariate analysis used, which carried out two compared variables. Results Based results study, 127 samples studied, 101 patients 26 declared cured. observed often among male than female patients. Among COVID-19, age groups dominated, namely, 17–25 (23.1%) > 64 groups. Moreover, most 26–35 group (23.8%). length treatment showed ≥ 6 months (82.2%) until these they cured 7–9 (61.5%). In who had type 2 DM (Diabetes Mellitus) 77.1%. Conclusions period significantly longer COVID-19.

Язык: Английский

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Are the integrin binding motifs within SARS CoV-2 spike protein and MHC class II alleles playing the key role in COVID-19?

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 10, 2023

The previous studies on the RGD motif (aa403-405) within SARS CoV-2 spike (S) protein receptor binding domain (RBD) suggest that integrin(s) may play an important role in infection of host cells. We also discussed possible two other integrin motifs are present S protein: LDI (aa585-587) and ECD (661-663), used by some viruses course infection. MultiFOLD models for structure analysis have shown is clearly accessible protein, whereas partially accessible. Furthermore, amino acids Epstein-Barr virus (EBV) gp42 playing very to HLA-DRB1 molecule subsequent immune response evasion, heptad repeat-2. Our model analyses these surface each chain as monomers homotrimer complex bind β chain. Therefore, they identical evasion EBV prediction MHC class II peptides core 9-mer peptide IRGDEVRQI HLA-DRB1*03:01 HLA-DRB3*01.01 strong 15-mer suggesting be potential epitope. Accordingly, infected or positive individuals develop high affinity anti-RGD antibodies react with proteins, like fibrinogen, thrombin von Willebrand factor, affecting haemostasis participating autoimmune disorders.

Язык: Английский

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COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

Archives of Clinical Trials, Год журнала: 2022, Номер 2(2)

Опубликована: Авг. 30, 2022

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