scholarly journals Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication

2021 ◽  
Vol 14 (11) ◽  
pp. 1111
Author(s):  
Ilona Bereczki ◽  
Henrietta Papp ◽  
Anett Kuczmog ◽  
Mónika Madai ◽  
Veronika Nagy ◽  
...  
Keyword(s):  
Cathepsin L ◽  
Antiviral Effect ◽  
Food Additive ◽  
New Drugs ◽  
Computational Studies ◽  
Mechanistic Studies ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Main Protease ◽  
A Cell

The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2 in Vero E6 cells, using a cell viability assay and quantitative PCR of the viral RNA, confirming their micromolar inhibitory activity against viral replication. Interestingly, two of the parent apocarotenoids, bixin and β-apo-8’carotenoic acid, exerted remarkable anti-SARS-CoV-2 activity. Mechanistic studies involved cathepsin L and B, as well as the main protease 3CLPro, and the results were rationalized by computational studies. Glycopeptide conjugates show dual inhibitory action, while apocarotenoids have mostly cathepsin B and L affinity. Since teicoplanin is a marketed antibiotic and the natural bixin is an approved, cheap and widely used red colorant food additive, these readily available compounds and their conjugates as potential antivirals are worthy of further exploration.

scholarly journals In vitro evaluation of the activity of terpenes and cannabidiol against Human Coronavirus E229

2021 ◽  
Author(s):  
Lior Chatow ◽  
Adi Nudel ◽  
Iris Nesher ◽  
David Hayo Hemo ◽  
Perri Rozenberg ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Host Cells ◽  
Lung Fibroblasts ◽  
Human Coronavirus ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
A Cell ◽  
Quantitative Results ◽  
Better Than

AbstractThe activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection. The combination of NT-VRL-1 with CBD potentiated the antiviral effect better than the positive controls pyrazofurin and glycyrrhizin. There was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect seen under the microscope after 72 h. To the best of our knowledge, this is the first report of activity of a combination of terpenes and CBD against a coronavirus.

scholarly journals In Vitro Evaluation of the Activity of Terpenes and Cannabidiol against Human Coronavirus E229

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 290
Author(s):  
Lior Chatow ◽  
Adi Nudel ◽  
Iris Nesher ◽  
David Hayo Hemo ◽  
Perri Rozenberg ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Host Cells ◽  
Lung Fibroblasts ◽  
Human Coronavirus ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
A Cell ◽  
Quantitative Results ◽  
Better Than

The activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The main constituents in the terpene formulation used for the experiment were beta caryophyllene, eucalyptol, and citral. The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection. The combination of NT-VRL-1 with CBD potentiated the antiviral effect better than the positive controls pyrazofurin and glycyrrhizin. There was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect seen under the microscope after 72 h. To the best of our knowledge, this is the first report of activity of a combination of terpenes and CBD against a coronavirus.

scholarly journals A2AR Antagonists Upregulate Expression of GS and GLAST in Rat Hypoxia Model

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jun Yu ◽  
Yan Yan ◽  
Yiye Chen ◽  
Yan Zheng ◽  
Xiaoyan Yu ◽  
...  
Keyword(s):  
Müller Cells ◽  
Muller Cells ◽  
Cell Viability Assay ◽  
Hypoxic Conditions ◽  
Viability Assay ◽  
Drug Concentrations ◽  
A Cell ◽  
Short Time

Background. The aim of this study was to research the effects of glutamine synthetase (GS) and glutamate aspartate transporter (GLAST) in rat Müller cells and the effects of an adenosine A2AR antagonist (SCH 442416) on GS and GLAST in hypoxia both in vivo and in vitro. Methods. This study used RT-PCR and Western blotting to quantify the expressions of GS and GLAST under different hypoxic conditions as well as the expressions of GS and GLAST at different drug concentrations. A cell viability assay was used to assess drug toxicity. Results. mRNA and protein expression of GS and GLAST in hypoxia Group 24 h was significantly increased. mRNA and protein expressions of GS and GLAST both increased in Group 1 μM SCH 442416 compared with other groups. One micromolar SCH 442416 could upregulate GS and GLAST’s activity in hypoxia both in vivo and in vitro. Conclusions. Hypoxia activates GS and GLAST in rat retinal Müller cells in a short time in vitro. (2) A2AR antagonists upregulate the activity of GS and GLAST in hypoxia both in vivo and in vitro.

A Cell Viability Assay Based on Monitoring Respiration by Optical Oxygen Sensing

2000 ◽  
Vol 278 (2) ◽  
pp. 221-227 ◽  
Author(s):  
Tomás C. O'Riordan ◽  
Deirdre Buckley ◽  
Vladimir Ogurtsov ◽  
Rosemary O'Connor ◽  
Dmitri B. Papkovsky
Keyword(s):  
Cell Viability ◽  
Oxygen Sensing ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
A Cell

scholarly journals Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery

2017 ◽  
Vol 8 ◽  
pp. 1218-1230 ◽  
Author(s):  
Liga Saulite ◽  
Dominyka Dapkute ◽  
Karlis Pleiko ◽  
Ineta Popena ◽  
Simona Steponkiene ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
Cell Viability Assay ◽  
Ki67 Expression ◽  
Lineage Differentiation ◽  
Viability Assay ◽  
Late Endosomes ◽  
Early Endosomes ◽  
A Cell

Nanotechnology-based drug design offers new possibilities for the use of nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated quantum dots QD655 were studied in human skin MSCs. The effect of QD on MSCs was examined using a cell viability assay, Ki67 expression analysis, and tri-lineage differentiation assay. The optimal conditions for QD uptake in MSCs were determined using flow cytometry. The QD uptake route in MSCs was examined via fluorescence imaging using endocytosis inhibitors for the micropinocytosis, phagocytosis, lipid-raft, clathrin- and caveolin-dependent endocytosis pathways. These data showed that QDs were efficiently accumulated in the cytoplasm of MSCs after incubation for 6 h. The main uptake route of QDs in skin MSCs was clathrin-mediated endocytosis. QDs were mainly localized in early endosomes after 6 h as well as in late endosomes and lysosomes after 24 h. QDs in concentrations ranging from 0.5 to 64 nM had no effect on cell viability and proliferation. The expression of MSC markers, CD73 and CD90, and hematopoietic markers, CD34 and CD45, as well as the ability to differentiate into adipocytes, chondrocytes, and osteocytes, were not altered in the presence of QDs. We observed a decrease in the QD signal from labelled MSCs over time that could partly reflect QD excretion. Altogether, these data suggest that QD-labelled MSCs could be used for targeted drug delivery studies.

scholarly journals Boceprevir, calpain inhibitors II and XII, and GC-376 have broad-spectrum antiviral activity against coronaviruses in cell culture

2020 ◽  
Author(s):  
Yanmei Hu ◽  
Chunlong Ma ◽  
Tommy Szeto ◽  
Brett Hurst ◽  
Bart Tarbet ◽  
...  
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Cathepsin L ◽  
Antiviral Drug ◽  
Antiviral Effect ◽  
Neutralization Assay ◽  
Drug Candidates ◽  
Main Protease ◽  
Human Coronaviruses ◽  
Calpain Inhibitors

AbstractAs the COVID-19 pandemic continues to fold out, the morbidity and mortality are increasing daily. Effective treatment for SARS-CoV-2 is urgently needed. We recently discovered four SARS-CoV-2 main protease (Mpro) inhibitors including boceprevir, calpain inhibitors II and XII and GC-376 with potent antiviral activity against infectious SARS-CoV-2 in cell culture. Despite the weaker enzymatic inhibition of calpain inhibitors II and XII against Mpro compared to GC-376, calpain inhibitors II and XII had more potent cellular antiviral activity. This observation promoted us to hypothesize that the cellular antiviral activity of calpain inhibitors II and XII might also involve the inhibition of cathepsin L in addition to Mpro. To test this hypothesis, we tested calpain inhibitors II and XII in the SARS-CoV-2 pseudovirus neutralization assay in Vero E6 cells and found that both compounds significantly decreased pseudoviral particle entry into cells, indicating their role in inhibiting cathepsin L. The involvement of cathepsin L was further confirmed in the drug time-of-addition experiment. In addition, we found that these four compounds not only inhibit SARS-CoV-2, but also SARS-CoV, MERS-CoV, as well as human coronaviruses (CoVs) 229E, OC43, and NL63. The mechanism of action is through targeting the viral Mpro, which was supported by the thermal shift binding assay and enzymatic FRET assay. We further showed that these four compounds have additive antiviral effect when combined with remdesivir. Altogether, these results suggest that boceprevir, calpain inhibitors II and XII, and GC-376 are not only promising antiviral drug candidates against existing human coronaviruses, but also might work against future emerging CoVs.

Evaluation of the Influence of Ferrite Magnetic Nanoparticle for Cancer Cell

2021 ◽  
Vol 323 ◽  
pp. 146-151
Author(s):  
Khishigdemberel Ikhbayar ◽  
Nomin Myagmar ◽  
Gantulga Davaakhuu ◽  
Uyanga Enkhnaran ◽  
Enkhmend Bekhbaatar ◽  
...  
Keyword(s):  
Cell Viability ◽  
Colony Formation ◽  
Magnetic Nanoparticle ◽  
In Vitro Cytotoxicity ◽  
Colony Formation Assay ◽  
Cell Viability Assay ◽  
Cytotoxic Effects ◽  
Viability Assay ◽  
A Cell

Magnetic nanoparticles for thermotherapy must be biocompatible and possess high thermal efficiency as heating elements. The biocompatibility of Mg 0.8 Ni 0.2 Fe 2 O 4 nanoparticles was studied using a cytotoxicity colony formation assay and a cell viability assay. HeLa cells exhibited cytotoxic effects when exposed to three different concentrations of 150 μg /ml, 100 μg /ml, and 50 μg /ml nanoparticles. Therefor e, c oncentrations of 50 μg /ml showed the lowest cytotoxic activity and the lowest toxicity to living cells. In vitro cytotoxicity of samples was then investigated by two methods, colony formation assay and cell viability assay. The Hela inhibited cell growth as 16.8% during heating by magnetic field generators.

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