Genome Biology and Evolution, Год журнала: 2023, Номер 15(4)
Опубликована: Апрель 1, 2023
Язык: Английский
iScience, Год журнала: 2023, Номер 26(11), С. 108319 - 108319
Опубликована: Окт. 24, 2023
Язык: Английский
Процитировано
16
PLoS ONE, Год журнала: 2024, Номер 19(4), С. e0301330 - e0301330
Опубликована: Апрель 3, 2024
The ongoing COVID-19 pandemic has led to the emergence of new SARS-CoV-2 variants as a result continued host-virus interaction and viral genome mutations. These have been associated with varying levels transmissibility disease severity. We investigated phenotypic profiles six (WT, D614G, Alpha, Beta, Delta, Omicron) in Calu-3 cells, human lung epithelial cell line. In our model demonstrated that all variants, except for Omicron, had higher efficiency virus entry compared wild-type. Delta variant greatest advantage terms early infection kinetics marked syncytia formation, which could facilitate cell-to-cell spreading, while Omicron displayed slower replication fewer formation. also identified strongest inducer inflammatory biomarkers, including pro-inflammatory cytokines/chemokines (IP-10/CXCL10, TNF-α, IL-6), anti-inflammatory cytokine (IL-1RA), growth factors (FGF-2 VEGF-A), these mediators were not significantly elevated infection. findings are consistent observations there was generally more pronounced response angiogenesis activity within lungs patients well severe symptoms mortality rate during wave, less lower observed current wave Thailand. Our suggest infectivity kinetics, enhanced specific mediator production may serve predictive indicators virulence potential future variants.
Язык: Английский
Процитировано
2
Advanced Healthcare Materials, Год журнала: 2024, Номер 13(19)
Опубликована: Апрель 27, 2024
Abstract In viral infections, natural killer (NK) cells exhibit anti‐viral activity by inducing apoptosis in infected host and impeding replication through heightened cytokine release. Extracellular vesicles derived from NK (NK‐EVs) also contain the membrane composition, homing capabilities, cargo that enable activity. These characteristics, their biocompatibility low immunogenicity, give NK‐EVs potential to be a viable therapeutic platform. This study characterizes size, EV‐specific protein expression, cell internalization, biocompatibility, miRNA evaluate properties of NK‐EVs. After 48 h NK‐EV incubation inflamed A549 lung epithelial cells, or conditions mimic infections such as during COVID‐19, treated with upregulated (miR‐27a, miR‐27b, miR‐369‐3p, miR‐491‐5p) compared non‐treated controls control EVs cells. Additionally, effectively reduce expression RNA pro‐inflammatory (TNF‐α, IL‐8) levels SARS‐CoV‐2 Vero E6 kidney mice without causing tissue damage while significantly decreasing controls. Herein, this work elucidates safe, nanomaterials, offering promising alternative conventional therapies.
Язык: Английский
Процитировано
2
Revista Brasileira de Farmacognosia, Год журнала: 2024, Номер 34(5), С. 883 - 898
Опубликована: Апрель 8, 2024
Язык: Английский
Процитировано
1
ACS Pharmacology & Translational Science, Год журнала: 2023, Номер 6(10), С. 1340 - 1346
Опубликована: Июль 6, 2023
The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that prodrugs varied different lines. In present study, we investigated profiles two tenofovir alafenamide (TAF) sofosbuvir (SOF) five lines commonly used research, namely, Vero E6, Huh-7, Calu-3, A549, Caco-2. We found TAF SOF were activated cell-dependent manner with E6 being least efficient Huh-7 most line for activating prodrugs. also demonstrated was at significantly higher rate than SOF. further analyzed protein expressions enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding relevant drug transporters P-glycoprotein organic anion-transporting polypeptides 1B1 1B3 using proteomics data extracted from literature proteome database. results revealed significant differences expression patterns among lines, which might partially contribute observed These findings highlight variability abundance between emphasize importance selecting appropriate assessing efficacy nucleoside/nucleotide
Язык: Английский
Процитировано
3
Pathogens, Год журнала: 2023, Номер 12(11), С. 1373 - 1373
Опубликована: Ноя. 20, 2023
The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in late 2019 and rapidly spread worldwide, becoming a pandemic that infected millions of people significant deaths. continues to be major threat, there is need deepen our understanding virus its mechanisms infection. To study cellular responses SARS-CoV-2 infection, we performed an RNA sequencing vs. uninfected Calu-3 cells. Total was extracted from (0.5 MOI) control cells converted cDNA. Sequencing performed, obtained reads were quality-analyzed pre-processed. Differential expression assessed with EdgeR package, functional enrichment EnrichR for Gene Ontology, KEGG pathways, WikiPathways. A total 1040 differentially expressed genes found cells, which 695 up-regulated 345 down-regulated. Functional analyses revealed predominant up-regulation related innate immune response, response virus, inflammation, cell proliferation, apoptosis. These transcriptional changes following infection may reflect help elucidate pathogenesis, addition revealing potential biomarkers drug targets.
Язык: Английский
Процитировано
3
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Ноя. 6, 2023
Abstract Understanding viral evolutionary dynamics is crucial to pandemic responses, informing prediction of virus adaptation over time, antiviral and immune pressures, design effective therapies, surveillance for public health strategies. Whole-genome sequencing (WGS) SARS-CoV-2 has enabled fine-grained studies evolution in the human population. Serial passaging vitro offers a complementary controlled environment investigate emergence persistence genetic variants that may confer selective advantage. In this study, nine lineages, including four "variants concern" three former under investigation", were sampled ≥33 serial passages (range 33-100) Vero E6 cells. WGS was used examine identify key mutations with implications fitness and/or transmissibility. Mutations accumulated regularly during passaging. Many low-frequency lost but others became fixed, suggesting either benefits, or at least lack deleterious effect. arose convergently both across passage lines compared contemporaneous clinical sequences, some hypothesised drive lineage success through host evasion (e.g. S:A67V, S:H655Y). The appearance these suggested can arise even absence multicellular response mechanisms other than immune-driven mutation. Such provide benefits viruses , stochastically. Our quantitative investigation into spans greatest number date, will inform measures reduce effects infection on Importance ongoing challenged efforts minimise impacts COVID-19 pandemic. Carrying out whole-genome outbreak cases global contact tracing identification concern within virus’ genome. Here, we use approach charting cell culture environment, focusing different lineages. demonstrates how continues evolve readily vitro, many changes mirroring those seen globally. Findings study are important investigating arise, considering future trajectory SARS-CoV-2.
Язык: Английский
Процитировано
2
Microorganisms, Год журнала: 2024, Номер 12(8), С. 1503 - 1503
Опубликована: Июль 23, 2024
Convalescent sera, rich in pathogen-specific antibodies, offers passive immunity to patients with infectious diseases. Screening assays using convalescent sera are crucial for evaluating therapeutic efficacy, selecting suitable serum donors, and standardizing assays. They measure antibody levels, neutralizing potential, specificity against viruses like SARS-CoV-2, ensuring contains potent antibodies. Standardized procedures enable reliable results wider adoption of therapy COVID-19. We have developed a high-content image-based assay screening SARS-CoV-2 variants. Using various cell lines, we identified optimal candidates, employed immunofluorescence visualize infected cells, assessed efficacy. potential activity Dose-response analysis showed variable activity, some exhibiting broad neutralization. Additionally, explored the synergy between β-d-N4-hydroxycytidine (NHC), an initial metabolite molnupiravir. These enhance therapy's benefits COVID-19 treatment aid understanding variants, addressing viral challenges.
Язык: Английский
Процитировано
0
Опубликована: Авг. 13, 2024
Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain var-iants spread more easily and are contagious, pose significant health menaces to global populations. The Malaysian isolates Alpha, Beta, Delta, Omicron were studied in Vero E6 cell line. Their deter-mined using plaque assay, quantitative real-time PCR (qRT-PCR), viral growth curve. Beta variant exhibited highest rate at 24 hours post-infection (h.p.i), as evi-denced by titers lowest RNA multiplication threshold. phenotypes also varied among variants, which formed largest smallest plaques, respectively. All showed strong cytopathic effects after 48 h.p.i. whole-genome sequencing highlighted cell-culture adaptation, where Delta acquired mutations multibasic cleavage site three cycles passaging. findings suggest a link between rates their respec-tive transmissibility pathogenicity. This is essential predicting impacts upcom-ing on local populations useful designing preventive measures curb virus outbreaks.
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10541 - 10541
Опубликована: Сен. 30, 2024
Comprehending the replication kinetics of SARS-CoV-2 variants helps explain why certain spread more easily, are contagious, and pose a significant health menace to global populations. The Malaysian isolates Alpha, Beta, Delta, Omicron were studied in Vero E6 cell line. Their determined using plaque assay, quantitative real-time PCR (qRT-PCR), viral growth curve. Beta variant exhibited highest rate at 24 h post-infection (h.p.i), as evidenced by titers lowest RNA multiplication threshold. phenotypes also varied among variants, which formed largest smallest plaques, respectively. All showed strong cytopathic effects after 48 h.p.i. whole-genome sequencing highlighted cell-culture adaptation, where acquired mutations multibasic cleavage site three cycles passaging. findings suggest link between rates their respective transmissibility pathogenicity. This is essential predicting impacts upcoming on local populations useful designing preventive measures curb virus outbreaks.
Язык: Английский
Процитировано
0