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https://www.readbyqxmd.com/read/28299152/ebola-viral-disease-in-west-africa-a-threat-to-global-health-economy-and-political-stability
#1
Semeeh Akinwale Omoleke, Ibrahim Mohammed, Yauba Saidu
The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences...
August 17, 2016: Journal of Public Health in Africa
https://www.readbyqxmd.com/read/28277549/the-final-oral-ebola-vaccine-trial-on-captive-chimpanzees
#2
Peter D Walsh, Drishya Kurup, Dana L Hasselschwert, Christoph Wirblich, Jason E Goetzmann, Matthias J Schnell
Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28240606/anticancer-kinase-inhibitors-impair-intracellular-viral-trafficking-and-exert-broad-spectrum-antiviral-effects
#3
Elena Bekerman, Gregory Neveu, Ana Shulla, Jennifer Brannan, Szu-Yuan Pu, Stanley Wang, Fei Xiao, Rina Barouch-Bentov, Russell R Bakken, Roberto Mateo, Jennifer Govero, Claude M Nagamine, Michael S Diamond, Steven De Jonghe, Piet Herdewijn, John M Dye, Glenn Randall, Shirit Einav
Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28231247/favipiravir-pharmacokinetics-in-ebola-infected-patients-of-the-jiki-trial-reveals-concentrations-lower-than-targeted
#4
Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec, Géraldine Piorkowski, Sara Carazo, Mamoudou N Conde, Jean-Luc Gala, Joseph Akoi Bore, Caroline Carbonnelle, Frédéric Jacquot, Hervé Raoul, Denis Malvy, Xavier de Lamballerie, France Mentré
BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28225767/interferon-%C3%AE-1a-for-the-treatment-of-ebola-virus-disease-a-historically-controlled-single-arm-proof-of-concept-trial
#5
Mandy Kader Konde, Darren P Baker, Fode Amara Traore, Mamadou Saliou Sow, Alioune Camara, Alpha Amadou Barry, Doussou Mara, Abdoulaye Barry, Moussa Cone, Ibrahima Kaba, Amento Ablam Richard, Abdoul Habib Beavogui, Stephan Günther, Melania Pintilie, Eleanor N Fish
To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit...
2017: PloS One
https://www.readbyqxmd.com/read/28216179/the-17th-international-congress-on-infectious-diseases-workshop-on-developing-infection-prevention-and-control-resources-for-low-and-middle-income-countries
#6
Sangeeta Sastry, Nadia Masroor, Gonzalo Bearman, Rana Hajjeh, Alison Holmes, Ziad Memish, Britta Lassmann, Didier Pittet, Fiona Macnab, Rachel Kamau, Evelyn Wesangula, Paras Pokharel, Paul Brown, Frances Daily, Fatma Amer, Jaime Torres, Miguel O'Ryan, Revathi Gunturu, Andre Bulabula, Shaheen Mehtar
Hospital-acquired infections (HAIs) are a major concern to healthcare systems around the world. They are associated with significant morbidity and mortality, in addition to increased hospitalization costs. Recent outbreaks, including those caused by the Middle East respiratory syndrome coronavirus and Ebola virus, have highlighted the importance of infection control. Moreover, HAIs, especially those caused by multidrug-resistant Gram-negative rods, have become a top global priority. Although adequate approaches and guidelines have been in existence for many years and have often proven effective in some countries, the implementation of such approaches in low- and middle-income countries (LMICs) is often restricted due to limited resources and underdeveloped infrastructure...
February 16, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28160722/molecular-modeling-simulation-and-docking-study-of-ebola-virus-glycoprotein
#7
Nasir Ahmad, Aqsa Farman, Syed Lal Badshah, Ata Ur Rahman, Haroon Ur Rashid, Khalid Khan
Ebola virus (EBOV) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. In this study secreted glycoprotein (Q7T9E0) of Ebola virus was acquired from Uniprot. The formation of alpha helix and beta sheets of secondary structures were predicted through online servers. Higher flexibility and disordered regions of proteins were determined through RONN, GLOBPLOT and DISSEMBLE...
March 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28152588/a-sensitive-in-vitro-high-throughput-screen-to-identify-pan-filoviral-replication-inhibitors-targeting-the-vp35-np-interface
#8
Gai Liu, Peter J Nash, Britney Johnson, Colette Pietzsch, Ma Xenia G Ilagan, Alexander Bukreyev, Christopher F Basler, Terry L Bowlin, Donald T Moir, Daisy W Leung, Gaya K Amarasinghe
The 2014 Ebola outbreak in West Africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting Ebola virus (EBOV). Within the EBOV replication complex, the interaction between polymerase cofactor, viral protein 35 (VP35), and nucleoprotein (NP) is critical for viral RNA synthesis. We recently identified a peptide at the N-terminus of VP35 (termed NPBP) that is sufficient for interaction with NP and suppresses EBOV replication, suggesting that the NPBP binding pocket can serve as a potential drug target...
March 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28117364/selective-inhibition-of-ebola-entry-with-selective-estrogen-receptor-modulators-by-disrupting-the-endolysosomal-calcium
#9
Hanlu Fan, Xiaohong Du, Jingyuan Zhang, Han Zheng, Xiaohui Lu, Qihui Wu, Haifeng Li, Han Wang, Yi Shi, George Gao, Zhuan Zhou, Dun-Xian Tan, Xiangdong Li
The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095824/community-based-health-care-is-an-essential-component-of-a-resilient-health-system-evidence-from-ebola-outbreak-in-liberia
#10
Kendra Siekmans, Salim Sohani, Tamba Boima, Florence Koffa, Luay Basil, Saïd Laaziz
BACKGROUND: Trained community health workers (CHW) enhance access to essential primary health care services in contexts where the health system lacks capacity to adequately deliver them. In Liberia, the Ebola outbreak further disrupted health system function. The objective of this study is to examine the value of a community-based health system in ensuring continued treatment of child illnesses during the outbreak and the role that CHWs had in Ebola prevention activities. METHODS: A descriptive observational study design used mixed methods to collect data from CHWs (structured survey, n = 60; focus group discussions, n = 16), government health facility workers and project staff...
January 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28095476/a-systematic-review-of-ebola-treatment-trials-to-assess-the-extent-to-which-they-adhere-to-ethical-guidelines
#11
Thomas Richardson, Andrew McDonald Johnston, Heather Draper
BACKGROUND: Objective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct. Design: Systematic review and narrative analysis. METHODS AND FINDINGS: Data sources: MEDBASE and EMBASE databases were searched using a specific search strategy. The Cochrane database for systematic reviews, the PROSPERO database and trial registries were examined. A grey literature search and citation search were also carried out...
2017: PloS One
https://www.readbyqxmd.com/read/27959624/will-there-be-a-cure-for-ebola
#12
Anthony P Cardile, Travis K Warren, Karen A Martins, Ronald B Reisler, Sina Bavari
Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk-pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid-based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp)...
January 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27942512/treating-the-host-response-to-emerging-virus-diseases-lessons-learned-from-sepsis-pneumonia-influenza-and-ebola
#13
REVIEW
David S Fedson
There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases...
November 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27914852/a-call-to-strengthen-the-global-strategy-against-schistosomiasis-and-soil-transmitted-helminthiasis-the-time-is-now
#14
REVIEW
Nathan C Lo, David G Addiss, Peter J Hotez, Charles H King, J Russell Stothard, Darin S Evans, Daniel G Colley, William Lin, Jean T Coulibaly, Amaya L Bustinduy, Giovanna Raso, Eran Bendavid, Isaac I Bogoch, Alan Fenwick, Lorenzo Savioli, David Molyneux, Jürg Utzinger, Jason R Andrews
In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy...
February 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27902714/evaluation-of-the-activity-of-lamivudine-and-zidovudine-against-ebola-virus
#15
Yu Cong, Julie Dyall, Brit J Hart, Lisa Evans DeWald, Joshua C Johnson, Elena Postnikova, Huanying Zhou, Robin Gross, Oscar Rojas, Isis Alexander, Nicole Josleyn, Tengfei Zhang, Julia Michelotti, Krisztina Janosko, Pamela J Glass, Mike Flint, Laura K McMullan, Christina F Spiropoulou, Tim Mierzwa, Rajarshi Guha, Paul Shinn, Sam Michael, Carleen Klumpp-Thomas, Crystal McKnight, Craig Thomas, Ann E Eakin, Kathleen G O'Loughlin, Carol E Green, Paul Catz, Jon C Mirsalis, Anna N Honko, Gene G Olinger, Richard S Bennett, Michael R Holbrook, Lisa E Hensley, Peter B Jahrling
In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV...
2016: PloS One
https://www.readbyqxmd.com/read/27898018/combating-ebola-with-repurposed-therapeutics-using-the-cando-platform
#16
Gaurav Chopra, Sashank Kaushik, Peter L Elkin, Ram Samudrala
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27893999/ebola-virus-disease-an-update-on-current-prevention-and-management-strategies
#17
REVIEW
M A Trad, W Naughton, A Yeung, L Mazlin, M O'sullivan, N Gilroy, D A Fisher, R L Stuart
Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived...
January 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/27890675/synergistic-drug-combination-effectively-blocks-ebola-virus-infection
#18
Wei Sun, Shihua He, Carles Martínez-Romero, Jennifer Kouznetsova, Gregory Tawa, Miao Xu, Paul Shinn, Ethan G Fisher, Yan Long, Omid Motabar, Shu Yang, Philip E Sanderson, Peter R Williamson, Adolfo García-Sastre, Xiangguo Qiu, Wei Zheng
Although a group of FDA-approved drugs were previously identified with activity against Ebola virus (EBOV), most of them are not clinically useful because their human blood concentrations are not high enough to inhibit EBOV infection. We screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of three-drug combinations, toremifene-mefloquine-posaconazole and toremifene-clarithromycin-posaconazole, were identified that effectively blocked EBOV entry and were further validated for inhibition of live EBOV infection...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#19
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27880800/minimal-in-vivo-efficacy-of-iminosugars-in-a-lethal-ebola-virus-guinea-pig-model
#20
Joanna L Miller, Simon G Spiro, Stuart D Dowall, Irene Taylor, Antony Rule, Dominic S Alonzi, Andrew C Sayce, Edward Wright, Emma M Bentley, Ruth Thom, Graham Hall, Raymond A Dwek, Roger Hewson, Nicole Zitzmann
The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated...
2016: PloS One
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