Viruses, Vol. 11, Pages 338: Mechanism of Action of Methotrexate Against Zika Virus

Viruses, Vol. 11, Pages 338: Mechanism of Action of Methotrexate Against Zika Virus Viruses doi: 10.3390/v11040338 Authors: Sungjun Beck Zhe Zhu Michelli F. Oliveira Davey M. Smith Jeremy N. Rich Jean A. Bernatchez Jair L. Siqueira-Neto Zika virus (ZIKV), which is associated with microcephaly in infants and Guillain-Barré syndrome, reemerged as a serious public health threat in Latin America in recent years. Previous high-throughput screening (HTS) campaigns have revealed several potential hit molecules against ZIKV, including methotrexate (MTX), which is clinically used as an anti-cancer chemotherapy and anti-rheumatoid agent. We studied the mechanism of action of MTX against ZIKV in relation to its inhibition of dihydrofolate reductase (DHFR) in vitro using Vero and human neural stem cells (hNSCs). As expected, an antiviral effect for MTX against ZIKV was observed, showing up to 10-fold decrease in virus titer during MTX treatment. We also observed that addition of leucovorin (a downstream metabolite of DHFR pathway) rescued the ZIKV replication impaired by MTX treatment in ZIKV-infected cells, explaining the antiviral effect of MTX through inhibition of DHFR. We also found that addition of adenosine to ZIKV-infected cells was able to rescue ZIKV replication inhibited by MTX, suggesting that restriction of de novo synthesis adenosine triphosphate (ATP) pools suppresses viral replication. These results confirm that the DHFR pathway can be targe...
Source: Viruses - Category: Virology Authors: Tags: Communication Source Type: research

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Authors: Zhou S, Wei J, Wang Y, Liu X Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite clinical advances, the survival rate of patients with HCC remains low, as most patients are diagnosed with HCC when they are already at the advanced stage. Certain circular RNAs (circRNAs) are closely associated with the development of liver cancer. In the present study, a circRNA array was performed to screen differentially expressed circRNAs in HCC tissues. The further analysis focused on the newly identified circRNA_101237, the host gene of which, cyclin-dependent kin...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Li L, Zheng Y, Zheng Q, Jiang J Abstract The present study aimed to investigate the antiproliferative effect of embryonic stem cell-conditioned medium (ESC-CM) on the mouse liver cancer Hepa1-6 cells in vitro. Furthermore, in order to elucidate the underlying molecular mechanism, the microRNAs (miRNAs) in ESC-CM associated with the inhibition of Hepa1-6 proliferation were identified. Following the co-culture of ESC-CM and Hepa1-6 in Transwell chambers, the proliferation, cell cycle, apoptosis and associated protein expression were determined in Hepal-6 cells. Moreover, miRNA array analysis was employed to ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Bacteria in some tumors may hinder cancer treatments. (read more)
Source: Environmental Factor - NIEHS Newsletter - Category: Environmental Health Source Type: news
Publication date: Available online 31 March 2020Source: Actas Urológicas Españolas (English Edition)Author(s): D. Nieblas-Toscano, A.J. Arenas-Bonilla, J.F. Flores-Martín, F. Gutiérrez-Tejero, C. Velarde-Muñoz, C.I. Ramos-Alaminos, M.C. Salas-Moreno, R. Galisteo-Moya, J. Moreno-Jiménez
Source: Actas Urologicas Espanolas - Category: Urology & Nephrology Source Type: research
This report provides an in-depth look at public drug program spending in Canada, using the Canadian Institute for Health Information's (CIHI) National Prescription Drug Utilization Information System. Public drug program spending does not include spending on drugs dispensed in hospitals or on those funded through cancer agencies and other special programs. Public drug program spending increased by 6.8% in 2018, compared to an increase of 5.3% in 2017. The growth in 2018 was largely because of the introduction of Ontario Health Insurance Plan+ (OHIP+), which extended drug coverage to all Ontario residents age 24 years or y...
Source: Healthcare Quarterly - Category: International Medicine & Public Health Source Type: research
This article analyzes data on 28 indicators prioritized over these years and demonstrates that 25 have shown sustained improvement over time. The performance management approach, lessons learned and gaps in knowledge are described to inform future research and practice.
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In this study, an in silico screening of the National Cancer Institute (NCI) diversity set based on ZIKV NS3 helicase was performed using a molecular docking approach. Selected compounds with drug-like properties were subjected to cell-based antiviral assays resulting in the identification of two novel lead compounds (named Compounds 1 and 2). They inhibited ZIKV infection with IC50 values at the micro-molar level (8.5 μM and 15.2 μM, respectively). Binding mode analysis, absolute binding free energy calculation, and structure–activity relationship studies of these two compounds revealed their possi...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Conclusions Apart West Nile virus (78), thousands of congenital microcephaly cases, fetal brain tissue damage and neurological syndromes have been associated with ZIKV infection. Unfortunately, the epidemics of this mosquito born, and a relative stable virus is on a rise. Although congenital microcephaly is a rare disorder however, due to lack of standardized diagnostic test facilities, the incidence in the geographically widespread ZIKV epidemic regions is higher. Animals studies showed that ZIKV is a neurotropic virus. It directly targets the developing embryonic brain cells by inducing apoptosis, cell-cycle arrest, and...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Study suggests diagnosis by EEG could be used instead of functional magnetic resonance imaging Related items from OnMedica ‘Silent’ heart attacks may affect one in 16 people Mammogram readers don ’t get less accurate with time Scans show severe brain damage in Zika-affected babies Study suggests Zika virus link to Guillain-Barr é syndrome Beam therapy hope for childhood cancer treatment
Source: OnMedica Latest News - Category: UK Health Source Type: news
I’ve hacked my way through a lot of jungles. I also live and practice medicine in South Florida. So I’m pretty familiar with mosquitoes. Apart from the itchy bumps and skin irritation that even a “normal” bite brings, mosquitoes can spread malaria, yellow fever, dengue fever, West Nile virus and, of course, the Zika virus. The problem is that Western medicine’s answer to the Zika public health scare is to kill off mosquitoes with man-made poisons that are far more dangerous than the virus. Governments in a number of countries, including the U.S., are now even thinking about bringing back DDT,...
Source: Al Sears, MD Natural Remedies - Category: Complementary Medicine Authors: Tags: Natural Cures zika virus Source Type: news
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