The Accessory Protein ORF3a Hijacks CLCC1 Chloride Channel to Cause ER Dysfunction in Beta-coronavirus Pathogenesis DOI Creative Commons
Liang Guo, Baoying Huang, Hanzhi Yu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Abstract The endoplasmic reticulum (ER) homeostasis is crucial for host cells and influenced by beta-coronaviruses upon invasion. However, the mechanisms which viral proteins interact with ER-resident factors to modulate ER functions morphology remain poorly understood. accessory protein ORF3a of SARS-CoV-2 plays a pivotal role in pathogenesis modulating immune responses. ER-localized chloride channel CLCC1 has been identified as strong interaction partner ORF3a, yet consequences this are not fully elucidated. Here, we demonstrate that interacts ion homeostasis, including increased luminal [Cl−], [K+], decreased [Ca2+], trigger unfolded ORF3a-CLCC1 linked phagy nucleophagy, monitored newly developed ratiometric reporters. Mechanistically, induces formation endogenous puncta, while overexpression attenuates ORF3a-associated toxicity sequestering within ER. Furthermore, conservation across suggests it potential therapeutic target uncovers ORF3a-mediated phenotypes spatiotemporally. In addition, expression mouse brains causes stress, phagy, endomembrane reorganization, shedding light on neurological manifestations long-term effects observed COVID-19 patients.

Language: Английский

The Yin and Yang of TLR4 in COVID-19 DOI
Suprabhat Mukherjee, Jagadeesh Bayry

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

5
A comprehensive review of current insights into the virulence factors of SARS-CoV-2 DOI Creative Commons

Yi Wang,

Bingqing Xia, Zhaobing Gao

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

ABSTRACT The evolution of SARS-CoV-2 pathogenicity has been a major focus attention. However, the determinants are still unclear. Various hypotheses have attempted to elucidate mechanisms underlying viral pathogenicity, but definitive conclusion yet be reached. Here, we review potential impact all proteins in on pathogenic process and analyze effects their mutations evolution. We aim summarize which virus-encoded crucial influencing defined as disease severity following infection. Mutations these key proteins, virulence factors SARS-CoV-2, may driving forces behind pathogenicity. S protein can entry fusogenicity. such NSP2, NSP5, NSP14, ORF7a alter virus’s ability suppress host synthesis innate immunity. NSP3, NSP4, NSP6, N protein, NSP12 replication efficiency. combined NSP6 significantly reduce replication. In addition, various including ORF3a, ORF8, Spike E directly participate inflammatory process. modulate levels inflammation Collectively, influence by impacting immune evasion, capacity, level mediated conclusion, is likely determined multiple factors.

Language: Английский

Citations

0
Exploring Serum and Glucocorticoid-Regulated Kinase 1: A Promising Target for COVID-19 and Atrial Fibrillation Treatment DOI Creative Commons

J. Fatima,

Faez Iqbal Khan, Jamal e Fatima

et al.

Heart Rhythm O2, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Pivotal roles of intracellular Cl− in COVID-19: pathogenesis and therapeutic targets DOI
Su Qu, Lei Chen,

Jie Sheng

et al.

Science Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Vitamin D: A Nutraceutical Supplement at the Crossroad Between Respiratory Infections and COVID-19 DOI Open Access
Manuela Rizzi, Pier Paolo Sainaghi

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2550 - 2550

Published: March 12, 2025

Even though in mid-2023 the World Health Organization declared end of public health emergency international concern status for COVID-19, many areas uncertainty about SARS-CoV-2 infection pathophysiology remain. Although last 4 years pharmaceutical industries widely invested development effective antiviral treatments and vaccines, large disparities their availability worldwide still exist, thus fostering investigation nutritional supplements as adjuvant therapeutic approaches disease management, especially resource-limited settings. During COVID-19 pandemic, vitamin D has been used an over-the-counter solution to improve evolution, thanks its known immunomodulatory anti-inflammatory actions. Ecological observational studies support a relationship between hypovitaminosis negative outcomes and, according this evidence, several research groups investigated role supplementation protecting from and/or improving evolution. This narrative review is intended offer insights into existing data on D’s biological effects respiratory infections, COVID-19. Furthermore, it will also brief overview complex interplay vaccine-elicited immune response, with special attention anti-COVID-19 vaccines.

Language: Английский

Citations

0
Vaccarin ameliorates osteoarthritis by suppressing the c-Jun N-terminal kinase (JNK)-serum amyloid A2 (SAA2) pathway mediating chondrocyte senescence DOI Creative Commons
Xin Gan, Jianwen Li,

Yongqiao Jiang

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156697 - 156697

Published: March 1, 2025

Osteoarthritis is a chronic degenerative joint disease marked by chondrocyte senescence and extracellular matrix degradation. Vaccarin, flavonoid with anti-inflammatory antioxidant properties, has not been previously investigated for its therapeutic potential in osteoarthritis. To evaluate the of Vaccarin osteoarthritis elucidate underlying mechanisms. This study utilized vitro cultures RNA sequencing to identify relevant pathways, followed validation at genetic, protein, metabolic levels using multiple approaches. Additionally, effects were assessed vivo destabilization medial meniscus (DMM)-induced mouse model human cartilage samples from patients. effectively ameliorated both vitro. Transcriptomic indicated significant downregulation serum amyloid A2 (SAA2) expression following treatment. Multi-omics analysis, validated specimens, that SAA2 minimally secreted healthy articular but serves as crucial biomarker Asian populations. Mechanistically, inhibits c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing mitigating inflammation senescence. Notably, inflammatory conditions upregulate chondrocytes via JNK pathway. Elevated contribute mitochondrial dysfunction chondrocytes, leading increased reactive oxygen species (ROS) production exacerbating progression. identifies target suggests presents promising treatment avenue.

Language: Английский

Citations

0
5-hydroxymethylcytosine Epigenetic Markers in COVID-19-Associated Acute Coronary Syndrome: Insights into Neutrophil Activation and PDE4D Upregulation DOI

Zhongheng Li,

Maimaitiyasen Duolikun,

Hangyu Chen

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract Background Studies have reported that 5hmC features in cell-free DNA (cfDNA) could serve as early warning biomarkers for the occurrence and progression of COVID-19, well myocardial injury. However, its roles acute coronary syndrome (ACS) following COVID-19 infection not been fully studied. Methods Firstly, we used 5hmC-Seal technique to obtain genome-wide profiles from plasma cfDNA 24 ACS2N patients (individuals experiencing ACS onset within 2 months after infection), 28 ACS2W beyond 16 (patients with without infection). Secondly, performed GO, KEGG analysis on differentially expressed genes identified a series immune inflammation related genes. Thirdly, distribution cells different groups was studied by infiltration analysis. Finally, PPI network these identify potential key target Results In this study, firstly found there significant difference levels between patients, while significant. it neutrophils were abnormally activated group. gene phosphodiesterase 4D (PDE4D) be highly group differential validated external datasets. Conclusions Our study suggested markers extracted differentiate patients. addition, observed exhibited abnormal activation Further showed may affect development up-regulating PDE4D expression.

Language: Английский

Citations

1
The SARS-CoV-2 envelope PDZ Binding Motif acts as a virulence factor disrupting host’s epithelial cell-cell junctions DOI Open Access
Flavio Alvarez, Guilherme Dias de Melo, Florence Larrous

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19 pandemic, has significantly impacted global health, emphasizing need to understand its pathogenicity and virulence mechanisms. SARS-CoV-2 disrupts alveolar epithelial barrier exacerbates airway inflammation, leading acute respiratory failure, but molecular details remain unclear. Additionally, infection causes neurological symptoms, potentially due weakly understood ability cross blood-brain barrier. The viral multifunctional Envelope (E) protein is crucial virulence, playing a key role in assembly, budding, release. E contains PDZ-binding motif (PBM) that interacts with host PDZ domain-containing proteins, affecting signaling pathways contributing pathogenicity. This study focuses on PBM disrupting barriers exacerbating inflammation. We generated recombinant mutant viruses lacking conducted both vitro vivo experiments elucidate impact fitness, pathogenicity, effects integrity. In vitro, mutants showed delayed replication reduced cytopathic effects. vivo, hamsters revealed PBM-deficient caused less weight loss, lower loads, indicating decreased Histological analyses confirmed damage these compared those infected wild-type virus. had impaired interactions tight junction proteins like ZO-1, PDZ-containing protein, maintaining Our findings also demonstrate does not play significant neuroinvasion during phase of infection, as evidenced by comparable RNA loads across brain regions hamsters, regardless presence. Histopathological transcriptomic further support this observation, suggesting primarily affects specific barriers. RNA-seq analysis lung brainstem from reveals modulates inflammatory immune responses, stronger tissue than brainstem. induce levels inflammation cytokine expression, PBM’s enhancing through activation such NF-κB TNF. Thus, plays critical SARS-CoV-2’s disruption cell junctions underscoring potential target therapeutic interventions.

Language: Английский

Citations

1
Evaluating tezepelumab for COPD: a missed target or unmet potential? DOI
Mario Cazzola, Paola Rogliani, Maria Gabriella Matera

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

0
Structural proteins of human coronaviruses: what makes them different? DOI Creative Commons

Nail Minigulov,

Kuandyk Boranbayev,

Ayaulym Bekbossynova

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Dec. 6, 2024

Following COVID-19 outbreak with its unprecedented effect on the entire world, interest to coronaviruses increased. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) is one seven that pathogenic humans. Others include SARS-CoV, MERS-CoV, HCoV-HKU1, HCoV-OC43, HCoV-NL63 and HCoV-229E. viruses differ in their pathogenicity. SARS-CoV-2 are capable spread rapidly cause epidemic, while HCoV-229E mild disease. difference viral behavior due structural functional differences. All human possess four proteins: spike, envelope, membrane, nucleocapsid. Spike protein receptor binding domain crucial for entry host cell, where different receptors cell recruited by viruses. Envelope plays important role assembly, following cellular entry, contributes immune response. Membrane an abundant protein, contributing assembly pathogenicity virus. Nucleocapsid encompasses RNA into ribonucleocapsid, playing replication. present review provides detailed summary characteristics proteins from coronaviruses, could serve as a practical reference when compared, novel treatments proposed.

Language: Английский

Citations

0