A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories

Viruses, Год журнала: 2025, Номер 17(2), С. 256 - 256

Опубликована: Фев. 13, 2025

In 2021, at the height of COVID-19 pandemic, coronavirus research spiked, with over 83,000 original articles related to word "coronavirus" added online resource PubMed. Just 2 years later, in 2023, only 30,900 were added. While, irrefutably, funding drastically decreased, a possible explanation for decrease interest is that projects on SARS-CoV-2, causative agent COVID-19, halted due challenge establishing good cellular or animal model system. Most laboratories do not have capabilities culture SARS-CoV-2 'in house' as this requires Biosafety Level (BSL) 3 laboratory. Until recently, BSL laboratory endemic coronaviruses was arduous low cytopathic effect isolated cell infection models and lack means quantify viral loads. The purpose review article compare human provide an assessment latest techniques use coronaviruses-HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1-as lower-biosafety-risk more pathogenic coronaviruses-SARS-CoV-2, SARS-CoV, MERS-CoV.

Язык: Английский

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Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells

Viruses, Год журнала: 2024, Номер 16(2), С. 212 - 212

Опубликована: Янв. 31, 2024

Viruses evolve many strategies to ensure the efficient synthesis of their proteins. One such strategy is inhibition integrated stress response—the mechanism through which infected cells arrest translation phosphorylation alpha subunit eukaryotic initiation factor 2 (eIF2α). We have recently shown that human common cold betacoronavirus OC43 actively inhibits eIF2α in response sodium arsenite, a potent inducer oxidative stress. In this work, we examined modulation responses by and demonstrated negative feedback regulator GADD34 strongly induced cells. However, upregulation expression was independent from activation not required for virus-infected Our work reveals complex interplay between coronavirus response, viral protein ensured but loop disrupted.

Язык: Английский

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SARS-CoV-2 and Coronaviruses: Understanding Transmission, Impact, and Strategies for Prevention and Treatment

Drugs and Drug Candidates, Год журнала: 2025, Номер 4(1), С. 5 - 5

Опубликована: Фев. 10, 2025

COVID-19, first identified in December 2019 Wuhan, China, is caused by the SARS-CoV-2 virus, a pathogen that primarily targets respiratory system and can lead to severe conditions such as acute distress syndrome (ARDS). Among seven coronaviruses known infect humans, three—SARS-CoV, MERS-CoV, SARS-CoV-2—are associated with illness significant morbidity. an enveloped, single-stranded RNA virus utilizes angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. The genetic sequence of highly mutable, leading emergence variants alter disease pathology transmission dynamics. World Health Organization (WHO) has classified these mutations into concern (VOCs), interest (VOIs), under monitoring (VUMs). This review provides in-depth analysis both historical emerging variants, summarizes recent advancements diagnostic methods detection, discusses current therapeutic strategies particular focus on virus-like particle (VLP) vaccines developed years. Additionally, we highlight ongoing approaches their implications managing COVID-19.

Язык: Английский

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Alveolar macrophages critically control infection by seasonal human coronavirus OC43 to avoid severe pneumonia

Cell Reports, Год журнала: 2025, Номер 44(4), С. 115531 - 115531

Опубликована: Апрель 1, 2025

Seasonal coronaviruses, similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), only cause symptoms in a small fraction of infected individuals. However, the host factors that determine variable responses infection remain unclear. Here, we use seasonal human OC43 (HCoV-OC43) as an asymptomatic model triggers both innate and adaptive immune mice. Interestingly, sensing pathways well cells are not essential protection against HCoV-OC43. Instead, alveolar macrophage (AMΦ) deficiency mice results COVID-19-like pneumonia post HCoV-OC43 infection, with abundant neutrophil infiltration, extracellular trap (NET) release, exaggerated pro-inflammatory cytokine production. Mechanistically, AMΦ efficiently phagocytose HCoV-OC43, effectively blocking virus spread, whereas, their absence, Toll-like receptor (TLR)-dependent chemokine production pneumonia. These findings reveal central role defending clinical implications for immunopathology associated infection.

Язык: Английский

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Contemporary seasonal human coronaviruses display differences in cellular tropism compared to laboratory-adapted reference strains

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 15, 2025

Abstract Seasonal human coronaviruses (sHCoVs) cause 15-30% of common colds. The reference strains used for research were isolated decades ago and have been passaged extensively but contemporary sHCoVs challenging to study as they are notoriously difficult grow in standard immortalized cell lines. Here we addressed these issues by utilizing primary nasal epithelial cells (HNECs) bronchial (BCi) differentiated at an air-liquid interface, well embryonic stem cell-derived alveolar type II (AT2) recover from nasopharyngeal specimens. From 21 specimens recovered four 229E, three NL63 eight OC43 viruses. All showed sequence differences lab-adapted CoVs, particularly within the spike gene. Evidence nucleotide changes receptor binding domains 229E detection recombination both isolates was also observed. Importantly, developed methods amplification high titre stocks that maintained identity, established titration sHCoV isolates. Comparison immortalised lines airway revealed tropism, growth kinetics cytokine production between strains. These data confirm differ and, using here, should be CoV biology evaluation medical countermeasures. Importance Zoonotic caused significant public health emergencies. occurrence a similar spillover event future is likely efforts further understand coronavirus priority. Several seasonal circulate population. Efforts viruses limited due difficulty isolating clinical Here, use cultures NL63, OC43. We establish make titrate show different tropism respiratory epithelium compared Although similarly infect epithelium, host response replication Using include when studying biology.

Язык: Английский

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Feasibility Study of Developing a Saline-Based Antiviral Nanoformulation Containing Lipid-Soluble EGCG: A Potential Nasal Drug to Treat Long COVID

Viruses, Год журнала: 2024, Номер 16(2), С. 196 - 196

Опубликована: Янв. 27, 2024

A recent estimate indicates that up to 23.7 million Americans suffer from long COVID, and approximately one workers may be out of the workforce each day due associated symptoms, leading a USD 50 billion annual loss salary. Post-COVID (Long COVID) neurologic symptoms are initial robust replication SARS-CoV-2 in nasal neuroepithelial cells, inflammation olfactory epithelium (OE) central nervous system (CNS), OE becoming persistent infection site. Previously, our group showed Epigallocatechin-3-gallate-palmitate (EC16) nanoformulations possess strong antiviral activity against human coronavirus, suggesting this green tea-derived compound nanoparticle formulations could developed as an intranasally delivered new drug eliminate infection, restored function reduced CNS. The objective current study was determine compatibility with primary epithelial cells (HNpECs). Methods: Nanoparticle size measured using ZetaView Tracking Analysis (NTA) system; contact determined by TCID50 assay for cytopathic effect on MRC-5 cells; post-infection inhibition HNpECs; cytotoxicity these MTT assay. rapid inactivation OC43 (a β-coronavirus) 229E (α-coronavirus) viruses further characterized transmission electron microscopy. Results: saline-based nanoformulation containing 0.1% w/v EC16 able inactivate 99.9999% β-coronavirus direct within 1 min. After 10-min incubation infected HNpECs formulation drug-grade (EGCG-4′ mono-palmitate or EC16m), viral inhibited 99%. In addition, all tested their cell viability were comparable normal saline, regularly used irrigation solution. 1-min either altered structure. Conclusion: Nanoformulations properties compatible application rapidly residing mucosa reduce CNS, pending additional safety studies.

Язык: Английский

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Mantis: high-throughput 4D imaging and analysis of the molecular and physical architecture of cells

PNAS Nexus, Год журнала: 2024, Номер 3(9)

Опубликована: Авг. 9, 2024

High-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell technologies: remote-refocus label-free microscopy oblique light-sheet fluorescence microscopy. Additionally, we shrimPy (Smart Robust Imaging Measurement in Python), an open-source software imaging, deconvolution, single-cell phenotyping data. Using Mantis shrimPy, achieved high-content correlative molecular dynamics the physical architecture 20 cell lines every 15 min over 7.5 h. This platform also facilitated detailed measurements impacts viral infection on host proteins. The can enable profiling intracellular dynamics, long-term analysis responses to perturbations, optical screens dissect gene regulatory networks.

Язык: Английский

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Mantis: high-throughput 4D imaging and analysis of the molecular and physical architecture of cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 19, 2023

Abstract High-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell technologies: remote-refocus label-free microscopy oblique light-sheet fluorescence microscopy. Additionally, we shrimPy, an open-source software imaging, deconvolution, single-cell phenotyping data. Using Mantis achieved high-content correlative molecular dynamics the physical architecture 20 cell lines every 15 minutes over 7.5 hours. This platform also facilitated detailed measurements impacts viral infection on host proteins. The can enable profiling intracellular dynamics, long-term analysis responses to perturbations, optical screens dissect gene regulatory networks. Significance Statement Understanding interactions components crucial biological research drug discovery. Current methods only image few fluorescent labels, providing limited view these processes. developed 3D maps among systems. combines multiple fluorophores with quantitative complemented by our data acquisition high-performance analysis. enabled simultaneous time-lapse perturbations like at resolution. approach accelerate image-based

Язык: Английский

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Anastrozole Protects against Human Coronavirus Infection by Ameliorating the Reactive Oxygen Species–Mediated Inflammatory Response

Antioxidants, Год журнала: 2024, Номер 13(1), С. 116 - 116

Опубликована: Янв. 17, 2024

The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen drug candidates against SARS-CoV-2. We determined antiviral effects FDA/EMA-approved anastrozole (AZ) on two coronaviruses, HCoV-OC43 HCoV-229E, using MRC-5 cells in vitro. AZ exhibited HCoV-229E infection. Subsequent studies focused which is related SARS-CoV-2 family. anti-viral reduced secretion inflammatory cytokines, TNF-α, IL-6, IL-1β. It also inhibited NF-κB translocation effectively suppress response. intracellular calcium reactive oxygen species (ROS) levels, including mitochondrial ROS Ca2+, induced by virus. expression NLRP3 inflammasome components cleaved IL-1β, suggesting that it blocks activation HCoV-OC43-infected cells. Moreover, enhanced cell viability gasdermin D (GSDMD), a marker pyroptosis. Overall, we demonstrated activity HCoV-229E. specifically its efficacy showed potential reduce inflammation, inhibit activation, mitigate dysfunction, pyroptosis infected

Язык: Английский

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Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment

Опубликована: Апрель 30, 2024

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in nasal neuroepithelial cells, leading to inflammation central nervous sys-tem (CNS). As today, there is no evidence that vaccines or medications can clear viral olfactory mucosa. Recently published clinical data demonstrate only 5% anosmia patients have fully recovered during past 2 years and 10.4% are still symptomatic 18 months post infection. Our group demonstrated ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting infection, well oxidative stress CNS, resto-ration neurologic functions. The objective current study evaluate mucociliary safety EC16m efficacy coronavirus. Meth-ods: size Zeta potential were measured using ZetaView Nanoparticle Tracking Analysis system; was determined MucilAir Human Nasal Epi-thelium Model; contact activity post-infection inhibition OC43 strain assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: saline-based EC16 mucoadhesive containing 0.005 0.02% w/v significant difference comparison saline (0.9% NaCl) tissue integrity, cytotoxicity, cilia beat fre-quency. A 5-minute inactivated 99.9% β-coronavirus OC43. replication inhibited >99% after infected MAR-5 cells treated one formulations. Con-clusion: novel rapidly coronavirus measurements comparable saline, a solution widely used applications.

Язык: Английский

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