Myocarditis associated with COVID-19 vaccination

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 28, 2024

Following the start of COVID-19 vaccination campaign, adverse events myocarditis and pericarditis were linked mainly to mRNA vaccines by regulatory authorities worldwide. have been administered several million people risk post has characterised in great detail. At present time research data available are scarce there is still no clear understanding biological mechanism/s responsible for this disease. This manuscript provides a concise overview epidemiology most prominent mechanistic insights pathophysiology Most importantly it underscores needed next steps agenda required characterize disease post-COVID-19 vaccination. Finally, shares our perspectives considerations public health.

Language: Английский

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Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination

Journal of the American Academy of Dermatology, Journal Year: 2023, Volume and Issue: 89(4), P. 685 - 693

Published: May 15, 2023

Language: Английский

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Key allosteric and active site residues of SARS-CoV-2 3CLpro are promising drug targets

Biochemical Journal, Journal Year: 2023, Volume and Issue: 480(11), P. 791 - 813

Published: May 31, 2023

The main protease of SARS-CoV-2, 3-chymotrypsin-like (3CLpro), is a prominent target for antiviral development due to its essential role in the viral life cycle. Research has largely focused on competitive inhibitors 3CLpro that active site. However, allosteric sites distal peptide substrate-binding region are also potential targets design reversible noncompetitive inhibitors. Computational analyses have examined importance key contacts at 3CLpro, but these not been validated experimentally. In this work, four druggable pockets spanning surface SARS-CoV-2 were predicted: pocket 1 site, whereas 2, 3, and 4 located away from site interface domains II III. Site-directed alanine mutagenesis selected residues with important structural interactions revealed 7 13 (N28, R40, Y54, S147, Y161, D187 Q192) 12 (T111, R131, N133, D197, N203, D289 D295) maintaining catalytically thermodynamically stable 3CLpro. Alanine substitution amino acid inactivated or reduced activity addition, thermodynamic stability decreased presence some mutations. This work provides experimental validation could be targeted as new therapeutics against COVID-19.

Language: Английский

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Identifying a causal link between prolactin signaling pathways and COVID-19 vaccine-induced menstrual changes

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 1, 2023

COVID-19 vaccines have been instrumental tools in the fight against SARS-CoV-2 helping to reduce disease severity and mortality. At same time, just like any other therapeutic, were associated with adverse events. Women reported menstrual cycle irregularity after receiving vaccines, this led renewed fears concerning their effects on fertility. Herein we devised an informatics workflow explore causal drivers of response vaccination mRNA vaccine BNT162b2. Our methods relied gene expression analysis vaccination, followed by network biology derive testable hypotheses regarding links between BNT162b2 irregularity. Five high-confidence transcription factors identified as BNT162b2-induced irregularity, namely: IRF1, STAT1, RelA (p65 NF-kB subunit), STAT2 IRF3. Furthermore, some biomarkers including TNF, IL6R, IL6ST, LIF, BIRC3, FGF2, ARHGDIB, RPS3, RHOU, MIF, topological genes predicted network-based mechanism reconstruction results indicated that exerted biological similar those resulting from prolactin signaling. However, these short-lived didn't raise concerns about long-term infertility issues. This approach can be applied interrogate functional drugs/vaccines side effects.

Language: Английский

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Safety of COVID-19 Vaccines in Patients with Autoimmune Diseases, in Patients with Cardiac Issues, and in the Healthy Population

Pathogens, Journal Year: 2023, Volume and Issue: 12(2), P. 233 - 233

Published: Feb. 2, 2023

The coronavirus disease 2019 (COVID-19) has been a challenge for the whole world since beginning of 2020, and COVID-19 vaccines were considered crucial eradication. Instead producing classic vaccines, some companies pointed to develop products that mainly function by inducing, into host, production antigenic protein SARS-CoV-2 called Spike, injecting an instruction based on RNA or DNA sequence. Here, we aim give overview safety profile actual known adverse effects these in relationship with their mechanism action. We discuss use at-risk people, especially those autoimmune diseases previously reported myocarditis, but also general population. debate real necessity administering unclear long-term people conditions, as well healthy at time omicron variants. This, considering existence therapeutic interventions, much more clearly assessed present compared past, relatively lower aggressive nature new viral

Language: Английский

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Systematic review and meta-analysis of myocarditis and pericarditis in adolescents following COVID-19 BNT162b2 vaccination

npj Vaccines, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 9, 2023

Abstract Myocarditis and pericarditis are frequent complications of COVID-19, but have also been reported following vaccination against COVID-19 in adolescents. To build vaccine confidence inform policy, we characterized the incidence myocarditis/pericarditis adolescents BNT162b2 explored association with dose sex. We searched national international databases for studies reporting as primary endpoint. The intra-study risk bias was appraised, random-effects meta-analyses were performed to estimate pooled by stratified 4.5 (95%CI: 3.14–6.11) per 100,000 vaccinations across all doses. Compared 1, significantly higher after 2 (RR: 8.62, 95%CI: 5.71–13.03). However, experienced a low booster than 0.06; 0.04–0.09). Males approximately seven times 6.66, 4.77–4.29) more likely females present myocarditis/pericarditis. In conclusion, found frequency BNT162b2, which occurred predominantly second male prognosis appears be favorable, full recovery both males females. National programs recommended adopt causality framework reduce overreporting, undercuts value on adolescent life, well extend inter-dose interval has linked lower

Language: Английский

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Assessing Therapeutic Value and Side Effects of Key Botanical Compounds for Optimized Medical Treatments

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Abstract Due to the significance of variable chemical groups across a wide spectrum modern medicine, it is imperative determine what most widely used group in medical applications with fewest side effects. Ten compounds from ten that are commonly known for their uses were compared terms therapeutic potential and The comparison among selected indicated superiority flavonoids over other multitude utilizations lower Kaempferol quercetin showed higher utilization Whereas alkaloid lowest levels use highest Based on conducted, concluded give priority flavonoid being because they exhibit Within flavonoids, kaempferol two highly recommended be widest range applications. Serious caution should considered before applying alkaloids any service. Understanding characteristics these can aid developing safer more effective treatments medicinal plants.

Language: Английский

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Unraveling the Anticancer Potential of SSRIs in Prostate Cancer by Combining Computational Systems Biology and In Vitro Analyses

ACS Omega, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Selective serotonin reuptake inhibitors (SSRIs) are known to have anticancer activity against different types of cancer. In this study, an integrative informatics approach was applied identify compound and genetic perturbations that produce similar effects SSRIs formulate systems biology hypotheses biological pathways involved in the putative prostate An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay assessed antiproliferative drug combinations. Cell death mechanisms were studied using annexin V-FITC/PI staining, cell cycle analysis carried out by counterstaining with propidium iodide. Relative gene expression a real-time polymerase chain reaction (PCR). Computational results hypothesized could potentially exert cancer lines modulating apoptotic tumorigenesis significantly inhibiting growth cells time concentration-dependent manner. The combination cisplatin, 5-fluorouracil, raloxifene resulted either synergistic or additive effects. significant increase early late PC3 cells. Dapoxetine, paroxetine, sertraline arrest at G0/G1 phase. Treatment dapoxetine paroxetine decreases Bcl-2, CASP8, DR5, VEGF. At same time, Bcl-2 VEGF increases CASP8 DR5. Results revealed can act as agents cells, their is mediated through signaling pathways.

Language: Английский

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Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 568 - 568

Published: Feb. 19, 2023

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, existing antivirals suffer from major limitations regarding drug resistance a limited spectrum activity. In fact, approved directly acting antiviral (DAA) drugs, which interfere with proteins confer selectivity towards their targets but spectrum. Nowadays, host-targeted (HTAs) on rise, discovery development pipelines, academia pharmaceutical industry. These drugs target host involved virus life cycle considered promising alternatives to DAAs due broader lower potential resistance. Herein, we discuss an important class HTAs that modulate signal transduction pathways by targeting kinases. Kinases key enzymes control virus-host interactions. We also provide synopsis pipeline detailing kinase targets, types, therapeutic classes repurposed top developing organizations. Furthermore, detail design repurposing considerations, as well challenges, kinase-targeted antivirals, including choice binding sites, physicochemical properties, combinations.

Language: Английский

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How far are the new wave of mRNA drugs from us? mRNA product current perspective and future development

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 12, 2022

mRNA products are therapies that regulated from the post-transcriptional, pre-translational stage of a gene and act upstream protein synthesis. Compared with traditional small molecule drugs antibody drugs, had advantages simple design, short development cycle, strong target specificity, wide therapeutic field, long-lasting effect. were now widely used in treatment genetic diseases, tumors, viral infections, expected to become third major class after drugs. The delivery system technology was key ensuring efficacy safety which plays an important role protecting RNA structure, enhancing targeting ability, reducing dose drug delivery, toxic side effects. Lipid nanoparticles (LNP) most common for In recent years, have seen rapid development, number on market increasing each year. success commercializing vaccines has driven wave nucleic acid development. clinically oncology, infectious diseases worldwide, while domestic clinical focused COVID-19 vaccines, more scope future indication expansion.

Language: Английский

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