scholarly journals Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2123
Author(s):  
Luciana S. Fernandes ◽  
Milene L. da da Silva ◽  
Roberto S. Dias ◽  
Marcel S. da S. da S. Lucindo ◽  
Ítalo E. P. da da Silva ◽  
...  

Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as Aedes aegypti, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC50) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC50 = 21.5 µmol·L–1, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays.

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jun Yu ◽  
Yan Yan ◽  
Yiye Chen ◽  
Yan Zheng ◽  
Xiaoyan Yu ◽  
...  

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.


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

2017 ◽  
Vol 8 ◽  
pp. 1218-1230 ◽  
Author(s):  
Liga Saulite ◽  
Dominyka Dapkute ◽  
Karlis Pleiko ◽  
Ineta Popena ◽  
Simona Steponkiene ◽  
...  

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.


2021 ◽  
Author(s):  
Lior Chatow ◽  
Adi Nudel ◽  
Iris Nesher ◽  
David Hayo Hemo ◽  
Perri Rozenberg ◽  
...  

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.


2021 ◽  
Vol 323 ◽  
pp. 146-151
Author(s):  
Khishigdemberel Ikhbayar ◽  
Nomin Myagmar ◽  
Gantulga Davaakhuu ◽  
Uyanga Enkhnaran ◽  
Enkhmend Bekhbaatar ◽  
...  

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.


2016 ◽  
Vol 26 (16) ◽  
pp. 4003-4006 ◽  
Author(s):  
Payal Rana ◽  
Yvonne Will ◽  
Sashi Nadanaciva ◽  
Lyn H. Jones

1996 ◽  
Vol 7 (5) ◽  
pp. 253-260 ◽  
Author(s):  
D.L. Taylor ◽  
S.P. Ahmed ◽  
T.M. Brennan ◽  
J.-F. Navé ◽  
P. Casara ◽  
...  

MDL 74968 (9-[2-methylidene-3-(phosphonomethoxy)-propyl]guanine), a novel acyclonucleotide derivative of guanine, inhibited human immunodeficiency virus type 1 (HIV-1) replication in vitro with activity comparable to that of adefovir (PMEA; 9-(2-phosphonomethoxyethyl)adenine). MDL 74968 was investigated in combination with two licensed nucleoside analogues, zidovudine and didanosine, using a cell viability assay, and drug interactions were evaluated by the isobologram technique, by calculating combination indices and by the MacSynergy™ program. Inhibition of HIV-1 replication was only additive in both cases. MDL 74968 had equivalent antiviral activity against strains of HIV-1 HXB2 engineered to have mutations which conferred resistance to the nucleoside analogues lamivudine, didanosine and zidovudine and the non-nucleoside inhibitor of reverse transcriptase (RT) nevirapine, as against the wild type strain. Continued passage of HIV-1 RF in C8166 cells in the presence of MDL 74968 for 5 months (30 passages) failed to select drug resistant mutants. Continued passage of virus in the presence of the same concentration of adefovir for the same length of time selected a virus in a single culture, which was 3-fold resistant to adefovir and cross-resistant to MDL 74968. Genotypic characterization of this virus revealed a lysine to arginine exchange (AAA to AGA) at position 65 in the RT gene. This virus was not cross-resistant to either zidovudine or nevirapine but showed reduced sensitivity to zalcitabine, didanosine and lamivudine. Continued passage of HIV-1 RF in the presence of nevirapine or zidovudine, using similar experimental protocols selected drug resistant viruses after eight and 17 passages, respectively, but these viruses remained sensitive to adefovir and MDL 74968.


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