synergistic effects against e coli atcc 11303  (ATCC)

Journal: Journal of Medical Virology

Article Title: Preclinical Screening Platform Identifies Azatadine‐Dimaleate as a Potent Repurposed Therapeutic Against SARS‐CoV‐2 Infection

doi: 10.1002/jmv.70713

Figure Lengend Snippet: Validation of hits identifies Azatadine‐Dimaleate as a potent SARS‐CoV‐2 inhibitor. (A) Validation of the selected 40 single molecules identified in the initial drug screen. Each candidate underwent 7 serial dilutions of 1 in 2, starting at 20 µM to test their ability to diminish cytotoxicity in SARS‐CoV‐2‐infected Calu‐3 cells (PHE MOI = 0.1) at 72 hpi. Three days post infection CPE was measured as per Fig.‐1. Data is representative of the average of three separate repeat experiments. (B) Validation of antiviral activity of Azatadine‐Dimaleate in a 96 well plate format. Remdesivir and Azatadine‐Dimaleate underwent 7 serial dilutions of 1 in 2, from a starting concentration of 20 µM to test their ability to prevent cytotoxicity in SARS‐CoV‐2‐infected Calu‐3 cells (MOI = 0.1) at 72 hpi and EC50s with 95% confidence intervals were calculated using nonlinear regression analysis. Cytotoxicity profiles of the drugs were determined in parallel. (C) Single agent screen of 29 antihistamine drugs in Calu3 and Vero cells. Drugs were added at a concentration of 5 µM and cells were incubated for 24 h, followed by SARS‐COV‐2 infection (PHE MOI = 0.1). At 72 hpi, CPE was measured as per Fig.‐1. Data represents an average of 3 separate repeat experiments.

Article Snippet: Combination with Remdesivir synergistically enhanced antiviral activity, reducing the EC50 of both drugs by > 60%.

Techniques: Biomarker Discovery, Infection, Activity Assay, Concentration Assay, Incubation

Journal: Journal of Medical Virology

Article Title: Preclinical Screening Platform Identifies Azatadine‐Dimaleate as a Potent Repurposed Therapeutic Against SARS‐CoV‐2 Infection

doi: 10.1002/jmv.70713

Figure Lengend Snippet: Azatadine‐Dimaleate exhibits dose‐dependent antiviral activity and synergistic enhancement with Remdesivir. (A) Cell viability assessment in uninfected Calu‐3 cells treated with DMSO control, Azatadine‐Dimaleate (25 µM), Remdesivir (1 µM), or the combination (Remdesivir 1 µM + Azatadine 25 µM) for 72 h. No cytotoxic effects were observed with any treatment. (B) Release of infectious virus was quantified by plaque assay. Calu‐3 cells were pretreated with Azatadine‐Dimaleate (5 & 25 µM) or Remdesivir (1 µM) 24 h before infection with SARS‐CoV‐2 PHE (MOI = 0.1). (C) Levels of viral NSP12 RNA was measured by RT‐qPCR following treatment with Azatadine‐Dimaleate at (5 & 25 µM) or Remdesivir (1 µM) 24 h before infection with SARS‐CoV‐2 (PHE MOI = 0.1). Data bars represent mean ± SEM of n = 3 independent experiments. Statistical analysis by one‐way ANOVA, *** p ≤ 0.001 vs DMSO control. (D) A concentration gradient of Remdesivir, Azatadine‐Dimaleate, or combined drugs was used to determine EC50s with 95% confidence intervals for these conditions in infected Calu‐3 cells pretreated 24 h before infection (PHE MOI = 0.1), with either Remdesivir (starting at 5 µM), Azatadine‐Dimaleate (starting at 40 µM), or a combination of the two with Remdesivir (starting at 1 µM) and Azatadine‐Dimaleate (starting at 25 µM). DMSO alone was used as a negative control. At 72 hpi viral titres were determined by plaque assay. Data points represent an average of 3 separate repeat experiments ±SEM.

Article Snippet: Combination with Remdesivir synergistically enhanced antiviral activity, reducing the EC50 of both drugs by > 60%.

Techniques: Activity Assay, Control, Virus, Plaque Assay, Infection, Quantitative RT-PCR, Concentration Assay, Negative Control

Journal: Journal of Medical Virology

Article Title: Preclinical Screening Platform Identifies Azatadine‐Dimaleate as a Potent Repurposed Therapeutic Against SARS‐CoV‐2 Infection

doi: 10.1002/jmv.70713

Figure Lengend Snippet: Azatadine‐Dimaleate inhibits SARS‐CoV‐2 replication in well‐differentiated primary bronchial epithelial cells. (A) WD‐PBECs from 5 donors were infected with SARS‐CoV‐2 (MOI = 1). At 24 hpi cultures were rinsed apically to titrate released virus and treated with Remdesivir (1 µM) or Azatadine‐Dimaleate (25 µM) alone, or a combination of both (0.4 µM Remdesivir and 10 µM Azatadine‐Dimaleate) or DMSO, and freshly treated every 24 h thereafter. Apical rinses were repeated at 48, 72 and 96 hpi and virus titers determined by plaque assay. (B) Inhibition of viral NSP12 gene expression in SARS‐CoV‐2‐infected WD‐PBECs following Azatadine‐Dimaleate +/‐ Remdesivir treatment. RNA samples were harvested at 96 hpi from each condition in duplicate from WD‐PBECs and NSP12 RNA expression was analyzed using RT‐qPCR. The relative ratios were calculated in reference to a house keeping gene GAPDH using light cycler 96 software 1.1. The data value plotted for each donor in each condition is an average of 2 biological duplicate Transwells and 4 technical replicates.

Article Snippet: Combination with Remdesivir synergistically enhanced antiviral activity, reducing the EC50 of both drugs by > 60%.

Techniques: Infection, Virus, Plaque Assay, Inhibition, Gene Expression, RNA Expression, Quantitative RT-PCR, Software

Journal: Materials Today Bio

Article Title: Genetically engineered bio-composite mediated dual-modality imaging-guided synergistic chemo-FUAS for tumor therapy

doi: 10.1016/j.mtbio.2025.101928

Figure Lengend Snippet: Schematic illustration of multifunctional bio-composite for anti-tumor therapy with synergistic FUAS (a) The construction of GVs- Ec @p/D and injected it intravenously into mice. (b) Upon intravenous injection, the obtained GVs- Ec @p/D in the tumor target area for enhancing FUAS combined with chemotherapy. (c) Guidance of dual-modality imaging with the irradiation of FUAS.

Article Snippet: Synergistic agents (SAs) can enhance the ablation efficiency to improve cancer therapy, has attracted increasing attention.

Techniques: Injection, Imaging, Irradiation

Journal: Materials Today Bio

Article Title: Genetically engineered bio-composite mediated dual-modality imaging-guided synergistic chemo-FUAS for tumor therapy

doi: 10.1016/j.mtbio.2025.101928

Figure Lengend Snippet: Synergistic effect of GVs- Ec @p/D by FUAS. ( a ) Representative photographs of ablated bovine livers after FUAS irradiation. The red dotted circle marks the coagulative necrosis of bovine livers. ( b ) Quantitative analysis of the gray value of bovine livers after FUAS irradiation (n = 3 , ∗∗∗∗ p < 0.0001). ( c ) Schematic diagram of the treatment process of FUAS. ( d ) Quantitative analysis of necrotic volume after FUAS ablation of bovine livers (n = 3, ∗∗∗∗ p < 0.0001). ( e ) Coagulative necrosis of tumors by TTC staining after FUAS, the necrotic tissue appears gray and the normal tumor tissue is red (yellow dotted circle marks the necrotic tissue). ( f ) The gray values of tumor tissues in each group after FUAS (n = 5, ∗∗ p < 0.01, -∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001). ( g ) In vivo USI of tumor tissues before and after FUAS ablation in different groups. The yellow dotted circle marks the tumor nodules. ( h ) The coagulative necrosis of tumor tissues in each group after FUAS (n = 5, ∗∗∗∗ p < 0.0001). ( i ) The EEF of tumor tissues in each group after FUAS (n = 5, ∗∗∗ p < 0.001, -∗∗∗∗ p < 0.0001). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Synergistic agents (SAs) can enhance the ablation efficiency to improve cancer therapy, has attracted increasing attention.

Techniques: Irradiation, Staining, In Vivo

Journal: Materials Today Bio

Article Title: Genetically engineered bio-composite mediated dual-modality imaging-guided synergistic chemo-FUAS for tumor therapy

doi: 10.1016/j.mtbio.2025.101928

Figure Lengend Snippet: In vivo synergistic chemo-FUAS therapy efficacy. ( a ) The protocol of the treatment regimen. ( b )Photos of tumors at the 16th day after treatment. ( c ) Relative tumor volume of different groups (n = 5, ∗∗∗∗ P < 0.0001). ( d ) Tumor weight on the 16th day (n = 5, ∗∗ P < 0.01, ∗∗∗ P < 0.001, ∗∗∗∗ P < 0.0001). The survival curves ( e ) and body weight ( f ) of mice in each group (n = 5). ( g ) Optical microscope images of tumor sections from each group were stained for H&E staining, PCNA, and TUNEL testing. Scale bar: 100 μm.

Article Snippet: Synergistic agents (SAs) can enhance the ablation efficiency to improve cancer therapy, has attracted increasing attention.

Techniques: In Vivo, Microscopy, Staining, TUNEL Assay