Chronic Shedding of a SARS-CoV-2 Alpha Variant Lineage Q.3/Q.4 in Wastewater DOI Open Access
Michael J. Conway, Hannah Yang,

Lauren A. Revord

et al.

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

Published: July 27, 2023

Abstract Central Michigan University (CMU) participated in a state-wide SARS-CoV-2 wastewater monitoring program since 2021. Wastewater samples were collected from on-campus sites and nine off-campus treatment plants servicing small metropolitan rural communities. genome copies quantified using droplet digital PCR results reported to the health department. One rural, site consistently produced higher concentrations of copies. Samples this sequenced initially contained predominately Alpha variant lineage Q.3, which transitioned Q.4. Q.3/Q.4 was detected at beginning fall 2021 continued until summer 2023. Mutational analysis reconstructed genes revealed divergence Q.3 clinical sequence over time, including numerous mutations surface glycoprotein RBD NTD. We discuss possibility that chronic infection accumulated adaptive promoted long-term infection. This study reveals can enhance resolution rare events facilitate reconstruction viral genomes due relative lack contaminating sequences.

Language: Английский

The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view DOI Creative Commons
Mihai Lazăr, Mihai Săndulescu, Ecaterina Constanța Barbu

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 639 - 639

Published: March 13, 2024

SARS-CoV-2 infection is a significant health concern that needs to be addressed not only during the initial phase of but also after hospitalization. This consequence various pathologies associated with long COVID-19, which are still being studied and researched. Lung fibrosis an important complication found in up 71% patients discharge. Our research based on scientific articles indexed PubMed; selection process, we used following keywords: “lung fibrosis”, “fibrosis mediators”, predictors”, “COVID-19”, “SARS-CoV-2 infection”, “long COVID-19”. In this narrative review, aimed discuss current understanding mechanisms initiation progression post-COVID-19 lung (PC-19-LF) risk factors for its occurrence. The pathogenesis pulmonary involves mediators such as TGF-β, legumain, osteopontin, IL-4, IL-6, IL-13, IL-17, TNF-α, Gal-1, Gal-3, PDGF, FGFR-1. key cellular effectors involved COVID-19 macrophages, epithelial alveolar cells, neutrophils, fibroblasts. main pathways include hypoxemia-induced fibrosis, macrophage-induced viral-fibroblast interaction-induced fibrosis.

Language: Английский

Citations

9
Chronic shedding of a SARS-CoV-2 Alpha variant in wastewater DOI Creative Commons
Michael J. Conway, Hannah Yang,

Lauren A. Revord

et al.

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

Published: Jan. 13, 2024

Central Michigan University (CMU) participated in a state-wide SARS-CoV-2 wastewater monitoring program since 2021. Wastewater samples were collected from on-campus sites and nine off-campus treatment plants servicing small metropolitan rural communities. genome copies quantified using droplet digital PCR results reported to the health department.

Language: Английский

Citations

6
SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19 DOI Creative Commons

Xiaoying Ma,

Jady Liang,

Guangheng Zhu

et al.

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of and the rare vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis thrombocytopenia; however, underlying mechanisms remain inadequately understood. Both infection vaccination utilize spike protein receptor-binding domain (RBD) SARS-CoV-2. We found that intravenous injection recombinant RBD significant platelet clearance in mice. Further investigation revealed could bind platelets, cause activation, potentiate aggregation, which was exacerbated Delta Kappa variants. RBD-platelet interaction partially dependent on β3 integrin as binding significantly reduced β3-/- Furthermore, to human mouse platelets related αIIbβ3 antagonists mutation RGD (arginine-glycine-aspartate) motif RGE (arginine-glycine-glutamate). developed anti-RBD polyclonal several monoclonal antibodies (mAbs) identified 4F2 4H12 for their potent dual inhibition RBD-induced vivo, replication Vero E6 cells. Our data show can though induce activation clearance, may contribute thrombocytopenia observed VITT. newly mAbs have potential not only diagnosis antigen but also importantly therapy against COVID-19.

Language: Английский

Citations

10
SARS-CoV-2 spike protein is a self-adjuvanted antigen for mucosal immunization and confers broad protection against lethal challenge with SARS-CoV-2 via intranasal vaccination DOI Creative Commons

Ping Zhao,

Zhendong Pan,

Zheng Xu

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Effective respiratory mucosal vaccines are urgently needed to control the rapid mutation and spread of SARS-CoV-2. In this respect, most focused virus vector-vaccine adjuvanted recombinant vaccine strategies face safety effectiveness concerns. Here, we revealed that spike protein (S-2P) original SARS-CoV-2 strain is a self-adjuvanted antigen for intranasal immunization can elicit potent systemic (serum IgG neutralizing antibodies splenic T-cell responses S1 S2 proteins) immunity (respiratory tract IgA responses) in absence an adjuvant. contrast, with hemagglutinin (HA) influenza H1N1 failed induce detectable serum antibodies. Furthermore, S-2P K18-hACE2 mice provided complete protection against lethal challenge 60% or 40% survival Omicron BA.5 EG.5, respectively. The immune induced by were significantly enhanced lentinan (LNT), immunomodulator used clinic, completely protected from EG.5 conferred additional protective mechanisms independent CD8 + T cells. Compared HA, robustly activated type I IFN signaling in vitro vivo, importantly, antibody response HA when it was simultaneously intranasally vaccinated HA. Mechanistically, integrins STING critically involved S-2P-eliciting via vaccination. Our findings demonstrate potential plus LNT as safe broad-spectrum variants.

Language: Английский

Citations

0
Cryo-electron microscopy in the fight against COVID-19—mechanism of virus entry DOI Creative Commons
Satish Bodakuntla,

Christopher Cyrus Kuhn,

Christian Biertümpfel

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Oct. 6, 2023

Cryogenic electron microscopy (cryo-EM) and tomography (cryo-ET) have become a critical tool for studying viral particles. Cryo-EM has enhanced our understanding of assembly replication processes at molecular resolution. Meanwhile, in situ cryo-ET been used to investigate how viruses attach invade host cells. These advances significantly contributed knowledge biology. Particularly, prompt elucidations structures the SARS-CoV-2 spike protein its variants directly impacted development vaccines therapeutic measures. This review discusses progress made by cryo-EM based technologies comprehending severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2), virus responsible devastating global COVID-19 pandemic 2020 with focus on mechanisms entry replication.

Language: Английский

Citations

9
Integrin α 5 β 1 contributes to cell fusion and inflammation mediated by SARS-CoV-2 spike via RGD-independent interaction DOI Creative Commons
Heng Zhang, Zhengli Wang,

Huong T. T. Nguyen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(50)

Published: Dec. 7, 2023

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infects host cells by engaging its spike (S) protein with human ACE2 receptor. Recent studies suggest the involvement of integrins in SARS-CoV-2 infection through interaction S protein, but underlying mechanism is not well understood. This study investigated role integrin α 5 β 1 , which recognizes Arg-Gly-Asp (RGD) motif physiological ligands, S-mediated entry and cell–cell fusion. Our results showed that does directly contribute to cell entry, it enhances fusion collaboration ACE2. effect cannot be inhibited putative inhibitor ATN-161 or high-affinity RGD-mimetic MK-0429 requires participation cytoplasmic tail (CT). We detected a direct between this rely on RGD-containing receptor binding domain S1 subunit protein. Instead, involves S2 homo-oligomerization. Furthermore, we found induces inflammatory responses endothelial cells, characterized NF-κB activation, gasdermin D cleavage, increased secretion proinflammatory cytokines IL-6 IL-1β. These effects can attenuated loss expression inhibition CT phosphodiesterase-4D (PDE4D), suggesting PDE4D pathway. findings provide molecular insights into pathogenesis mediated nonclassical RGD-independent ligand-binding signaling function potential targets for antiviral treatment.

Language: Английский

Citations

8
SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly DOI Creative Commons
Anna Onnis, Emanuele Andreano, Chiara Cassioli

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 220(2)

Published: Nov. 15, 2022

CTL-mediated killing of virally infected or malignant cells is orchestrated at the immune synapse (IS). We hypothesized that SARS-CoV-2 may target lytic IS assembly to escape elimination. show human CD8+ T upregulate expression ACE2, Spike receptor, during differentiation CTLs. CTL preincubation with Wuhan Omicron variants inhibits and function, as shown by defective synaptic accumulation TCRs tyrosine phosphoproteins well centrosome granule polarization IS, resulting in impaired cell cytokine production. These defects were reversed anti-Spike antibodies interfering ACE2 binding reproduced engagement angiotensin II anti-ACE2 antibodies, but not product Ang (1-7). also observed ex vivo CTLs from COVID-19 patients. results highlight a new strategy evasion based on Spike-dependent, ACE2-mediated targeting prevent elimination cells.

Language: Английский

Citations

14
Diverse Genetic Conflicts Mediated by Molecular Mimicry and Computational Approaches to Detect Them DOI Open Access
Shelbi L. Russell, Gabriel Penunuri,

Christopher Condon

et al.

Published: March 28, 2024

In genetic conflicts, driver and killer elements achieve biased survival, replication, or transmission over sensitive targeted through a wide range of molecular mechanisms, including mimicry. Driving mechanisms manifest at all organismal levels, from the propagation individual genes, as demonstrated by transposable elements, to genomes, illustrated viruses, cell lineages, in cancer. Targeted genomes are vulnerable mimicry conserved motifs they use for their own signaling regulation. Mimicking these enables selfish element control core target processes, can occur sequence, structure, functional level. Molecular was first appreciated an important phenomenon more than twenty years ago. Modern genomics technologies, databases, machine learning approaches offer tremendous potential study distribution across conflicts nature. Here, we explore theoretical expectations between conflicting trends known outline how new examples be gleaned population genomic datasets. We discuss mimics involving short sequence-based gene duplications evolve convergently mutations. Whereas, processes that involve divergent domains fully-folded structures among horizontal transfer. These largely based on small number organisms should reevaluated general, phylogenetically independent framework. Currently, publicly available databases mined genotypes driving non-mendelian inheritance patterns, epistatic interactions, convergent protein structures. A subset may mimics. propose detecting conflict

Language: Английский

Citations

2
Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin DOI Open Access
Sokolov Av, Irina Isakova–Sivak,

Daria Mezhenskaya

et al.

BioMetals, Journal Year: 2022, Volume and Issue: 36(3), P. 437 - 462

Published: Nov. 5, 2022

Language: Английский

Citations

10
Integrin αvβ1 facilitates ACE2-mediated entry of SARS-CoV-2 DOI Creative Commons

Zeqiong Cai,

Han Bai,

Doudou Ren

et al.

Virus Research, Journal Year: 2023, Volume and Issue: 339, P. 199251 - 199251

Published: Nov. 2, 2023

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed investigate how integrins facilitate ACE2-mediated cellular entry of SARS-CoV-2. We first tested susceptibility a panel human cell lines infection using spike protein pseudotyped virus assay and examined expression levels these by qPCR, western blot flow cytometry. found that integrin αvβ1 was highly enriched susceptible lines. Additional studies demonstrated RGD (403-405)→AAA mutant defective binding compared its wild type counterpart, anti-αvβ1 antibodies significantly inhibited into cells. Further mouse NIH3T3 cells expressing ACE2, αv, β1, and/or suggest unable function as an independent receptor could SASR-CoV-2. Finally, we observed Omicron exhibited significant increase viral entry. Our findings may enhance our understanding pathogenesis offer potential therapeutic target for COVID-19.

Language: Английский

Citations

4