Journal: BMC Biology

Article Title: Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy

doi: 10.1186/s12915-025-02132-y

Figure Lengend Snippet: Virtual screening of small molecules from the FDA-approved drug library. A Crystal structure of CD96 in complex with PVR (PDB Code: 6ARQ), with the binding interface highlighted in blue. B Detailed depiction of amino acids involved in the CD96/PVR interaction, with residues shown in stick representation. C Relationship between molecular weight and S-value for selected small molecules. Red indicates molecules with molecular weights between 250 and 700 and S-values of -5 or less. D-F Results of further screening of small molecules interacting with the CD96/PVR binding interface. G Distribution of S-values for the final 15 selected small molecules

Article Snippet: 1729 small molecules were obtained from FDA-approved drug library (Topscience, Shanghai, China).

Techniques: Drug discovery, Binding Assay, Molecular Weight

Journal: Cell communication and signaling : CCS

Article Title: BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, β-catenin- and MGMT-dependent apoptotic cell death.

doi: 10.1186/s12964-022-01007-x

Figure Lengend Snippet: Fig. 1 BMX, TMZ, oxaliplatin (Oxp) and doxorubicin (Dox) combination inhibited cell proliferation in CRC cells. (A) The proliferation of BMX, TMZ, Oxp, Dox, BMX plus TMZ, BMX plus Oxp or BMX plus Dox in HT29, HCT116 and RKO cells with various drug concentration. (B) Colony formation capability assay with different treatments of BMX, TMZ, Oxp, BMX plus TMZ, and BMX plus Oxp in HT29, HCT116 and RKO cells; the colonies were counted for quantification. (C) Cell cycle analysis after 48 h treatment with different concentrations of BMX alone or BMX combined with TMZ in HT29, HCT116, and RKO cells and the proportion of cells in each cell cycle phase. SubG1, cell with polyploid chromosome; > 4 N, polyploid cell. (D) Apoptosis analysis after 48 h treatment with different concentrations of BMX alone or BMX combined with TMZ and the apoptotic rate of cells in HT29, HCT116, and RKO cells. All results are shown as mean ± s.d. from three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 versus control (HT29 cells); #p < 0.05, ##p < 0.01, ###p < 0.001 vs. control (HCT116 cells); †p < 0.05, ††p < 0.01, †††p < 0.001 versus control (RKO cells)

Article Snippet: The cell proliferation of CRC cells was measured by CCK8 assay (Targetmol, Shanghai, China).

Techniques: Concentration Assay, Cell Cycle Assay, Control

Journal: Cell communication and signaling : CCS

Article Title: BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, β-catenin- and MGMT-dependent apoptotic cell death.

doi: 10.1186/s12964-022-01007-x

Figure Lengend Snippet: Fig. 5 BMX, VPA, SAHA, TMZ, Oxp, and Dox combination inhibited cell proliferation in CRC cells. (A) HDAC8 mRNA expression levels stimulated with BMX (5 µM), VPA (4 mM), SAHA (2 µM) with or without TMZ were determined using qRT-PCR assays. (B) HT29, HCT116, and RKO cells were treated with BMX with or without TMZ for 48 h. Then, cells were harvested for detection of acetyl-histone H3 (Lys9/Lys14), acetyl-histone H4 (Lys8), and HDAC8 by Western blot analysis. (C) The proliferation of BMX, VPA, SAHA with or without TMZ, Oxp (5 µM) and Dox (1 µM) in HT29, HCT116, and RKO cells with treatment durations were assayed using the CCK-8 method. (D) Colony formation capability assay with different treatments of BMX, VPA, SAHA with or without TMZ, Oxp and Dox in HT29, HCT116, and RKO cells; the colonies were counted for quantification. All results are shown as mean ± s.d. from three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 versus control (HT29 cells); #p < 0.05, ##p < 0.01, ###p < 0.001 versus control (HCT116 cells); †p < 0.05, ††p < 0.01, †††p < 0.001 versus control (RKO cells)

Article Snippet: The cell proliferation of CRC cells was measured by CCK8 assay (Targetmol, Shanghai, China).

Techniques: Expressing, Quantitative RT-PCR, Western Blot, CCK-8 Assay, Control

Journal: Cell communication and signaling : CCS

Article Title: BMX, a specific HDAC8 inhibitor, with TMZ for advanced CRC therapy: a novel synergic effect to elicit p53-, β-catenin- and MGMT-dependent apoptotic cell death.

doi: 10.1186/s12964-022-01007-x

Figure Lengend Snippet: Fig. 7 Autophagy expression levels stimulated with BMX and PCI-34051 in the presence or absence of TMZ. (A) HT29, HCT116, and RKO cells were treated with BMX and PCI-34051 with or without TMZ for 48 h. Then, cells were harvested for detection of acetyl-histone H3 (Lys9/Lys14), acetyl-histone H4 (Lys8), and HDAC8 by Western blot analysis. (B) The proliferation of BMX and PCI-34051 with or without TMZ in HT29, HCT116, and RKO cells. (C) Colony formation capability assay with different treatments of BMX and PCI-34051 with or without TMZ in HT29, HCT116, and RKO cells; the colonies were counted for quantification. (D, E) Expressions of cleaved caspase 3, cleaved PARP, LC3 and p62 proteins in HT29, HCT116, and RKO cells treated with BMX and PCI-34051 with or without TMZ for 48 h. All results are shown as mean ± s.d. from three independent experiments. *p < 0.05, **p < 0.01, ***p < 0.001 versus control (HT29 cells); #p < 0.05, ##p < 0.01, ###p < 0.001 versus control (HCT116 cells); †p < 0.05, ††p < 0.01, †††p < 0.001 versus control (RKO cells)

Article Snippet: The cell proliferation of CRC cells was measured by CCK8 assay (Targetmol, Shanghai, China).

Techniques: Expressing, Western Blot, Control

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: Schematic overview of the anti-SARS-CoV-2 drug screening procedure. ( a ) ACE2 targeted inhibitors and compounds from the natural product library were applied prior to infection with SARS-CoV-2 (pre-infection treatment) while compounds from the FDA-approved library and the flavonoid library were applied post infection (post- infection treatment). Out of 2191 compounds tested, 121 displayed viral CPE reductions and 7 were selected for further validations using Vero E6 and HuH7 cell lines and hNEC. ( b ) Uninfected cells, infected cells treated with 0.1% DMSO, and infected cells treated with remdesivir were included as controls in the screen. Following treatment with citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate, reduced CPE was observed when compared to the DMSO control.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Drug discovery, Infection, Control

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: Summary of compounds identified from the primary screen that exhibit potential antiviral effects against SARS-CoV-2 infection.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Infection, Reverse Transcription, Reflux

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: Validation of primary hits. For validating compounds with activity pre-infection, Vero E6 cells were first pre-treated with increasing concentrations of ( a ) citicoline, ( b ) pravastatin sodium and ( c ) tenofovir alafenamide prior to infection with SARS-CoV-2. Similarly, Huh7 cells were pre-treated with ( d ) citicoline, ( e ) pravastatin sodium and ( f ) tenofovir alafenamide and subsequently infected with SARS-CoV-2. For post-infection treatment validation, Vero E6 cells were infected with SARS-CoV-2 and treated with increasing concentrations of ( g ) imatinib mesylate, ( h ) calcitriol, ( i ) dexlansoprazole and ( j ) prochlorperazine dimaleate. Similarly, HuH7 cells were also infected then treated with a range of concentrations of ( k ) imatinib mesylate, ( l ) calcitriol, ( m ) dexlansoprazole and ( n ) prochlorperazine dimaleate. The primary and secondary exes correspond to the viral titre and relative cell viability, and the dashed line represents the CC 50 cut-off for cell viability. One-way ANOVA and Dunnett’s post-test were used to determine statistical differences, with * denoting p < 0.05, ** denoting p < 0.01 and *** denoting p < 0.001. Error bars represent the standard deviation observed from the means of triplicates performed for both cell viability and dose-dependent inhibition studies.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Biomarker Discovery, Activity Assay, Infection, Standard Deviation, Inhibition

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: Validation of primary hits in hNECs. Selected primary hits were further validated in hNECs. Cells were either pre-treated with 10 μM citicoline prior to SARS-CoV-2 infection or treated following SARS-CoV-2 infection with 10 μM imatinib mesylate and 10 μM calcitriol. One-way ANOVA and Dunnett’s post-test were used to determine statistical differences, with ** denoting that p < 0.01. Error bars represent the standard deviation observed from the means of triplicates performed for dose-dependent inhibition studies.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Biomarker Discovery, Infection, Standard Deviation, Inhibition

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: SARS-CoV-2 and calcitriol modulate vitamin D Receptor (VDR), 24-hydroxylase (24(OH)ase), and cathelicidin (LL-37) in Vero E6 and Huh7 cells. In the first part of the experiment, Vero E6 and Huh7 cells were either mock-infected with media, or SARS-CoV-2 infected and harvested at indicated timepoints in the absence of calcitriol for baseline VDR, 24(OH)ase, and LL-37 mRNA expression. Vero E6 expression of ( a ) VDR, ( b ) 24(OH)ase and ( c ) LL-37 and Huh7 expression of ( d ) VDR, ( e ) 24(OH)ase and ( f ) LL-37 were as shown. In the second part of the experiment, Vero E6 and Huh7 cells were either mock-infected with media or SARS-CoV-2 for 1 h as above, then treated with 0.01, 0.1, 1, 10 or 20 µM calcitriol following infection. At 48 h post infection, the cells were harvested to check for VDR, 24(OH)ase, and LL-37 mRNA expression. Vero E6 mRNA expression of ( g ) VDR, ( i ) 24(OH)ase and ( k ) LL-37 and Huh7 expression of ( h ) VDR, ( j ) 24(OH)ase and ( l ) LL-37 were as shown. Data are represented as relative quantity to 0.1% DMSO control, or as relative quantity to mock-infected control. One-way ANOVA and Dunnett’s post-test and paired t -test were used to determine statistical differences, with * denoting p < 0.05, ** denoting p < 0.01 and *** denoting p < 0.001. Error bars represent the standard deviation observed from the means of triplicates performed for mRNA expression studies.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Infection, Expressing, Control, Standard Deviation

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: Western blot analysis of SARS-CoV-2 spike and VDR proteins in Vero E6 cells. ( a ) Vero E6 cells are either mock infected with media (−) or with SARS-CoV-2 (+) for 1 h. After 1 h post-infection, the cells are then either untreated (−) or treated (+) with 20 µM calcitriol for 6-, 24- and 48- hours before harvesting of total cell lysate. ( b ) Densitometry quantitation of protein expression levels is shown as fold changes to beta-actin. Full-length blots are shown in .

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: Western Blot, Infection, Quantitation Assay, Expressing

Journal: Pharmaceutics

Article Title: Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants

doi: 10.3390/pharmaceutics15030925

Figure Lengend Snippet: In vivo study of calcitriol treatment. 8-week old K18-hACE2 male and female mice were separated into treatment and non-treatment groups. Treatment study group has been given 3 days pre-treatment and 5 days post-treatment of calcitriol (5 μg/kg) via intraperitoneal injection. The non-treatment group has been given a PBS as a treatment control. Next, 10 3 PFU of SARS-CoV-2 (L, Alpha, and Beta variants) were inoculated through intranasal delivery to all groups after pre-treatment. Physiological parameters: body weight ( a – c ), survival rate ( d – f ), and physiological conditions were monitored after infections. For comparison between individual physiological conditions, 5 dpi infected mice were compared between treatment groups of all three variant infected mice ( g – i ). Scoring of physiological conditions was based on five criteria: appearance of the mouse coat, level of consciousness, activity level, eye condition, and respiratory quality. To compare the severity of damage in mouse tissues after infection, left lung lobes from 4 dpi mice were processed for histological analyses and scored based on six criteria to determine severity ( j – l ). The six criteria are inflammatory cell infiltration, haemorrhage, oedema, bronchial epithelial cell damage, degeneration of alveolar epithelial cells, and parenchymal wall expansion. For viral load determination, right lung, brain, liver, and spleen tissues from the same 4 dpi mice were harvested and homogenised for virus titration ( m – o ). Data is not shown for liver and spleen tissues. Statistical significance is determined with a two-tailed unpaired t -test, with * denoting p < 0.05. Survival group: variant L: n = 6 (treatment and no treatment); Alpha: n = 6 (treatment), n = 4 (no treatment); Beta: n = 6 (treatment), n = 5 (no treatment). 4 dpi group: variant L: n = 7 (treatment and no treatment); Alpha and Beta: n = 5 each (treatment and no treatment). Mock infection, n = 3.

Article Snippet: A primary screen to identify novel compounds with potential antiviral effects against SARS-CoV-2 infection was performed on four different libraries, namely a 462-compound ACE2-targeted compound library (CADD) (TargetMol, Boston, MA, USA), a 57-compound natural product library, a 500-compound flavonoids library (TimTec, Tampa, FL, USA), and a 1172-compound FDA-approved drug library (Selleckchem, Houston, TX, USA).

Techniques: In Vivo, Injection, Control, Comparison, Infection, Variant Assay, Activity Assay, Virus, Titration, Two Tailed Test