17 research outputs found
Screening of melatonin, α-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity
No full textMOESM2 of Screening of melatonin, Îą-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity
No full textAdditional file 2. Effect of folic acid on DENV2 infection of HEK293T/17 and HepG2 cells
Discordant Activity of Kaempferol Towards Dengue Virus and Japanese Encephalitis Virus
No full textKaempferol, a plant-derived flavonoid, has been reported to have activity against Japanese encephalitis virus (JEV) in BHK-21 cells. To determine the broader utility of this compound, we initially evaluated the activity of kaempferol against JEV and dengue virus (DENV) in HEK293T/17 cells. Results showed no significant antiviral activity against either virus. We subsequently investigated the activity of kaempferol against both JEV and DENV in BHK-21 cells. Results showed a significant inhibition of JEV infection but, surprisingly, a significant enhancement of DENV infection. The effect of kaempferol on both host protein expression and transcription was investigated and both transcriptional and translational inhibitory effects were observed, although a more marked effect was observed on host cell protein expression. Markedly, while GRP78 was increased in DENV infected cells treated with kaempferol, it was not increased in JEV infected cells treated with kaempferol. These results show that cellular alteration induced by one compound can have opposite effects on viruses from the same family, suggesting the presence of distinct replication strategies for these two viruses
MOESM1 of Screening of melatonin, Îą-tocopherol, folic acid, acetyl-l-carnitine and resveratrol for anti-dengue 2 virus activity
No full textAdditional file 1. Effect of acetyl-l-carnitine on DENV2 infection of HEK293T/17 and HepG2 cells
Investigation of the activity of baicalein towards Zika virus
No full textAbstract Background Zika virus (ZIKV) is a mosquito transmitted virus spread primarily by Aedes species mosquitoes that can cause disease in humans, particularly when infection occurs in pregnancy where the virus can have a significant impact on the developing fetus. Despite this, there remains no prophylactic agent or therapeutic treatment for infection. Baicalein is a trihydroxyflavone, that is found in some traditional medicines commonly used in Asia, and has been shown to have several activities including antiviral properties. Importantly, studies have shown baicalein to be safe and well tolerated in humans, increasing its potential utilization. Methods This study sought to determine the anti-ZIKV activity of baicalein using a human cell line (A549). Cytotoxicity of baicalein was determined by the MTT assay, and the effect on ZIKV infection determined by treating A549 cells with baicalien at different time points in the infection process. Parameters including level of infection, virus production, viral protein expression and genome copy number were assessed by flow cytometry, plaque assay, western blot and quantitative RT-PCR, respectively. Results The results showed that baicalein had a half-maximal cytotoxic concentration (CC50) of > 800 µM, and a half-maximal effective concentration (EC50) of 124.88 µM. Time-of-addition analysis showed that baicalein had an inhibitory effect on ZIKV infection at the adsorption and post-adsorption stages. Moreover, baicalein also exerted a significant viral inactivation activity on ZIKV (as well as on dengue virus and Japanese encephalitis virus) virions. Conclusion Baicalein has now been shown to possess anti-ZIKV activity in a human cell line
Utilizing Quantitative Proteomics to Identify Species-Specific Protein Therapeutic Targets for the Treatment of Leishmaniasis
No full textLeishmaniasis is
a tropical disease caused by Leishmania parasites,
which are transmitted through the bites of infected sandflies.
We focused on the emergence of leishmaniasis in Thailand caused by
a species (Leishmania orientalis).
Treatment by chemotherapy is not effective against L. orientalis. Hence, we intended to solve this issue
using a proteomics approach to investigate protein profiles and in silico analysis for the identification of antigenic proteins
from L. orientalis, Leishmania martiniquensis, and Leishmania
donovani. Using principal component analysis (PCA),
protein profile comparisons indicated that different species of Leishmania are different at the protein level. Proteomics
analysis identified 6099 proteins. Among these proteins, 1065 proteins
were used for further analysis. There were 16 proteins that were promising
candidates for therapeutic aspects as they were abundantly expressed
and common to all species. In silico analysis of
protein’s antigenicity revealed that eight proteins had the
potential for the development of antigenic molecules. Protein profile
information and these antigenic proteins may play key roles in the
pathogeny of leishmaniasis and can be used as novel therapeutic targets
against leishmaniasis in the future
Expression of dengue virus and Zika virus NS2B-NS3pro constructs alter cellular fatty acids, but co-expression with a Zika virus virus-like particle is detrimental to virus-like particle expression
No full textAbstract Objective Studies have shown that Flavivirus infection remodels the host cell to favour viral replication. In particular, the host cell lipid profile is altered, and it has been proposed that this process alters membrane fluidity to allow wrapping of the outer structural proteins around the viral nucleocapsid. We investigated whether expression of the Zika virus (ZIKV) and dengue virus (DENV) protease induced alterations in the cellular lipid profile, and subsequently whether co-expression of these proteases with VLP constructs was able to improve VLP yield. Results Our results showed that both ZIKV and DENV proteases induced alterations in the lipid profile, but that both active and inactive proteases induced many of the same changes. Neither co-transfection of protease and VLP constructs nor bicistronic vectors allowing expression of both protease and VLP separated by a cell cleavable linker improved VLP yield, and indeed many of the constructs showed significantly reduced VLP production. Further work in developing improved VLP expression platforms is required
Evaluation of the antiviral activity of orlistat (tetrahydrolipstatin) against dengue virus, Japanese encephalitis virus, Zika virus and chikungunya virus
No full textMany mosquito transmitted viruses of the genera Alphavirus and Flavivirus are human pathogens of significant concern, and there is currently no specific antiviral for any member of these two genera. This study sought to investigate the broad utility of orlistat (tetrahydrolipstatin) in reducing virus infection for several mosquito borne viruses including flaviviruses (dengue virus (DENV; nine isolates analyzed), Japanese encephalitis virus (JEV; one isolate analyzed) and Zika virus (ZIKV; 2 isolates analyzed)) as well as an alphavirus (chikungunya virus; CHIKV; 2 isolates analyzed). Three different treatment regimens were evaluated, namely pre-treatment (only), post-treatment (only) and pre- and post-treatment, and three factors were evaluated, namely level of infection, virus titer and genome copy number. Results showed that all three treatment modalities were able to significantly reduce virus titer for all viruses investigated, with the exception of three isolates of DENV in the pre-treatment only regimen. Pre- and post-treatment was more effective in reducing the level of infection and genome copy number of all viruses investigated than either pre-treatment or post-treatment alone. Collectively, these results suggest orlistat has potential as a broad-spectrum agent against multiple mosquito transmitted viruses.</p
