In Vitro Evaluation of Antiviral Activities of Funicone-like Compounds Vermistatin and Penisimplicissin against Canine Coronavirus Infection

Antibiotics, Год журнала: 2023, Номер 12(8), С. 1319 - 1319

Опубликована: Авг. 15, 2023

Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional compounds named vermistatin (VER) and penisimplicissin (PS) investigated their inhibitory towards CCoV infection. Thus, both been tested for cytotoxicity A72 cells, fibrosarcoma cell line suitable investigating CCoV. Our findings showed an increase viability, with improvement morphological features CCoV-infected cells at non-toxic doses 1 μM VER 0.5 PS. In addition, observed these caused strong inhibition expression aryl hydrocarbon receptor (AhR), ligand-activated transcription factor is activated during results also alkalinization lysosomes presence or PS, may be involved activities.

Язык: Английский

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Shedding light on the cellular mechanisms involved in the combined adverse effects of fine particulate matter and SARS-CoV-2 on human lung cells

The Science of The Total Environment, Год журнала: 2024, Номер 952, С. 175979 - 175979

Опубликована: Сен. 2, 2024

Airborne pathogens represent a topic of scientific relevance, especially considering the recent COVID-19 pandemic. Air pollution, and particulate matter (PM) in particular, has been proposed as possible risk factor for onset spread pathogen-driven respiratory diseases. Regarding SARS-CoV-2 infection, exposure to fine PM (PM2.5, particles with an aerodynamic diameter < 2.5 μm) associated increased incidence disease. To provide useful insights into mechanisms through which might be involved we exposed human lung cells (A549) PM2.5 SARS-CoV-2, evaluate toxicological properties molecular pathways activated when airborne are combined viral particles. Winter was collected metropolitan urban area its physico-chemical composition analyzed. A549 were concomitantly or after pre-treatment PM2.5. Inflammation, oxidative stress xenobiotic metabolism main investigated. Results showed that 72 h significantly expression angiotensin-converting enzyme 2 (ACE2) receptor, is one keys used by virus infect host cells. We also analyzed endosomal route process internalization, studying RAB5 RAB7. The results show pre-activated then increased. activation inflammatory studied. Our findings increase pro-inflammatory markers (NF-kB IL-8) subsequently further 24 h, demonstrating interaction between determines severity responses epithelial In conclusion, study provides mechanistic biological evidence contribution progression diseases populations.

Язык: Английский

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Construction and validation of a mouse model for studying severe human adenovirus infections

Virologica Sinica, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to fatality, especially immunosuppressed patients, young children, military recruits. Currently, no vaccines or specific drugs approved for clinical use. The hosts of strictly species-specific, which strongly limits the development against HAdVs. In this study, immunocompetent BALB/c mice were challenged different doses human adenovirus type 5 (HAdV-5) via tail intravenous injection (i.v.). All a high dose HAdV-5 (3.2 ​× ​10

Язык: Английский

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Activation of Chaperone-Mediated Autophagy Inhibits the Aryl Hydrocarbon Receptor Function by Degrading This Receptor in Human Lung Epithelial Carcinoma A549 Cells

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(20), С. 15116 - 15116

Опубликована: Окт. 12, 2023

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and substrate protein of Cullin 4B E3 ligase complex responsible for diverse cellular processes. In the lung, this bioactivation benzo[a]pyrene during tumorigenesis. Realizing that AHR function affected by its expression level, we are interested in degradation mechanism lung. Here, have investigated using human lung epithelial A549 cells. We observed levels increase presence chloroquine (CQ), an autophagy inhibitor, dose-dependent manner. Treatment with 6-aminonicotinamide (6-AN), chaperone-mediated (CMA) activator, decreases concentration-dependent time-dependent This decrease suppresses ligand-dependent activation target gene transcription, can be reversed CQ but not MG132. Knockdown lysosome-associated membrane 2 (LAMP2), autophagy-related 5 (ATG5), chloroquine-mediated protein. resistant to CMA when motif mutated. Suppression epithelial-to-mesenchymal transition cells knocked out or level reduced 6-AN. Collectively, provided evidence supporting continuously undergoing

Язык: Английский

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Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 15, 2024

Summary Background Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The complete pathogenesis of the virus remains to be determined. Unraveling molecular mechanisms governing SARS-CoV-2 interactions with host cells crucial for formulation effective prophylactic measures and advancement COVID-19 therapeutics. Methods We analyzed human lung single-cell RNA sequencing dataset discern association butyrophilin subfamily 3 member A2 ( BTN3A2 ) expression COVID-19. gene edited cell lines transgenic mice were infected live in a biosafety level (BSL-3) laboratory. Immunoprecipitation, flow cytometry, biolayer interferometry competition ELISA assays performed cells. quantitative real-time PCR, histological and/or immunohistochemical analyses tissue samples from or without infection. Findings mRNA was correlated severity. predominantly identified epithelial cells, elevated pathological patients co-occurred ACE2 same subtypes. targeted early stage viral life cycle inhibiting attachment through receptor-binding domain (RBD) Spike protein ACE2. inhibited ACE2-mediated infection reducing vitro vivo . Interpretation These results reveal key role fight against Identifying potential monoclonal antibodies which mimic may facilitate disruption infection, providing therapeutic avenue Funding This study supported National Natural Science Foundation China (32070569, U1902215, 32371017), CAS “Light West China” Program, Yunnan Province (202305AH340006). Research context Evidence before this Our understanding COVID-19, especially events incompletely albeit we witnessed many progresses. knowledge gap hinders finding specific antiviral agents SARS-CoV-2. entry mediated receptor angiotensin-converting enzyme (ACE2) affected defenses. Targeting these universal factors required replication most promising approach prevention treatment Added value revealed that BTN3A2, primate-specific gene, acts as potent inhibitor up-regulation upon competed binding protein, subsequently entry. Implications all available evidence data highlighted novel factor protective effects holds considerable drug mitigating impact its variants concern (VOCs).

Язык: Английский

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