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https://www.readbyqxmd.com/read/27902714/evaluation-of-the-activity-of-lamivudine-and-zidovudine-against-ebola-virus
#1
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
#2
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
#3
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...
November 11, 2016: 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
#4
Wei Sun, Shihua He, Carles Martínez-Romero, Jennifer Kouznetsova, Gregory Tawa, Miao Xu, Paul Shinn, Ethan 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, 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...
November 24, 2016: 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
#5
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
#6
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
https://www.readbyqxmd.com/read/27879115/preface
#7
Avner Friedman, Mirosław Lachowicz, Urszula Ledzewicz, Monika Joanna Piotrowska, Zuzanna Szymanska
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#8
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27864075/the-natural-compound-silvestrol-is-a-potent-inhibitor-of-ebola-virus-replication
#9
Nadine Biedenkopf, Kerstin Lange-Grünweller, Falk W Schulte, Aileen Weißer, Christin Müller, Dirk Becker, Stephan Becker, Roland K Hartmann, Arnold Grünweller
The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation initiation complex in eukaryotes, is an important novel drug target in cancer research because its helicase activity is required to unwind extended and highly structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound isolated from the plant Aglaia foveolata, is a highly efficient, non-toxic and specific inhibitor of eIF4A. Importantly, 5'-capped viral mRNAs often contain structured 5'-UTRs as well, which may suggest a dependence on eIF4A for their translation by the host protein synthesis machinery...
November 15, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27849485/psychological-impact-of-deploying-in-support-of-the-u-s-response-to-ebola-a-systematic-review-and-meta-analysis-of-past-outbreaks
#10
Kartavya J Vyas, Eileen M Delaney, Jennifer A Webb-Murphy, Scott L Johnston
OBJECTIVE: To examine the potential psychological impact of deploying in support of the U.S. response to Ebola in west Africa by systematic review and meta-analysis. METHODS: Peer-reviewed articles published between January 2000 and December 2014 were identified using PubMed, PsycINFO, and Web of Science. Thirty-two studies involving 26,869 persons were included in the systematic review; 13 studies involving 7,785 persons were included in the meta-analysis. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated...
November 2016: Military Medicine
https://www.readbyqxmd.com/read/27799354/comprehensive-characterization-of-cellular-immune-responses-following-ebola-virus-infection
#11
Christine Dahlke, Sebastian Lunemann, Rahel Kasonta, Benno Kreuels, Stefan Schmiedel, My L Ly, Sarah K Fehling, Thomas Strecker, Stephan Becker, Marcus Altfeld, Abdourahmane Sow, Ansgar W Lohse, César Muñoz-Fontela, Marylyn M Addo
The West-African Ebola virus disease (EVD) outbreak was the largest EVD outbreak in history. However, data on lymphocyte dynamics and antigen-specificity of T-cells in Ebola survivors are scarce and our understanding of EVD-pathophysiology is limited.The care for an EVD-survivor, who cleared the infection without experimental drugs allowed for the detailed examination of lymphocyte dynamics. We demonstrate persistence of T-cell activation well beyond viral clearance and detect Ebola-specific T-cells. Our study provides significant insights into lymphocyte specificity during the re-convalescent phase of EVD and may inform novel strategies to treat EVD...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27792169/integrated-computational-approach-for-virtual-hit-identification-against-ebola-viral-proteins-vp35-and-vp40
#12
Muhammad Usman Mirza, Nazia Ikram
The Ebola virus (EBOV) has been recognised for nearly 40 years, with the most recent EBOV outbreak being in West Africa, where it created a humanitarian crisis. Mortalities reported up to 30 March 2016 totalled 11,307. However, up until now, EBOV drugs have been far from achieving regulatory (FDA) approval. It is therefore essential to identify parent compounds that have the potential to be developed into effective drugs. Studies on Ebola viral proteins have shown that some can elicit an immunological response in mice, and these are now considered essential components of a vaccine designed to protect against Ebola haemorrhagic fever...
October 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27771389/lassa-and-ebola-virus-inhibitors-identified-using-minigenome-and-recombinant-virus-reporter-systems
#13
Stephen R Welch, Lisa Wiggleton Guerrero, Ayan K Chakrabarti, Laura K McMullan, Mike Flint, Gregory R Bluemling, George R Painter, Stuart T Nichol, Christina F Spiropoulou, César G Albariño
Lassa virus (LASV) and Ebola virus (EBOV) infections are important global health issues resulting in significant morbidity and mortality. While several promising drug and vaccine trials for EBOV are ongoing, options for LASV infection are currently limited to ribavirin treatment. A major factor impeding the development of antiviral compounds to treat these infections is the need to manipulate the virus under BSL-4 containment, limiting research to a few institutes worldwide. Here we describe the development of a novel LASV minigenome assay based on the ambisense LASV S segment genome, with authentic terminal untranslated regions flanking a ZsGreen (ZsG) fluorescent reporter protein and a Gaussia princeps luciferase (gLuc) reporter gene...
October 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27764560/ebola-vaccines-in-clinical-trial-the-promising-candidates
#14
Yuxiao Wang, Jingxin Li, Yuemei Hu, Qi Liang, Mingwei Wei, Fengcai Zhu
Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial...
October 20, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27754861/deciphering-assumptions-about-stepped-wedge-designs-the-case-of-ebola-vaccine-research
#15
Adélaïde Doussau, Christine Grady
Ethical concerns about randomising persons to a no-treatment arm in the context of Ebola epidemic led to consideration of alternative designs. The stepped wedge (SW) design, in which participants or clusters are randomised to receive an intervention at different time points, gained popularity. Common arguments in favour of using this design are (1) when an intervention is likely to do more good than harm, (2) all participants should receive the experimental intervention at some time point during the study and (3) the design might be preferable for practical reasons...
October 17, 2016: Journal of Medical Ethics
https://www.readbyqxmd.com/read/27743917/modelling-ebola-virus-dynamics-implications-for-therapy
#16
Alexey Martyushev, Shinji Nakaoka, Kei Sato, Takeshi Noda, Shingo Iwami
Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals...
October 12, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27736754/favipiravir-pharmacokinetics-in-non-human-primates-insights-for-future-efficacy-studies-of-haemorrhagic-fever-viruses
#17
Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27733281/global-regional-and-national-life-expectancy-all-cause-mortality-and-cause-specific-mortality-for-249-causes-of-death-1980-2015-a-systematic-analysis-for-the-global-burden-of-disease-study-2015
#18
COMMENT
(no author information available yet)
BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010...
October 8, 2016: Lancet
https://www.readbyqxmd.com/read/27712998/inhibitors-of-retrograde-trafficking-active-against-ricin-and-shiga-toxins-also-protect-cells-from-several-viruses-leishmania-and-chlamydiales
#19
Neetu Gupta, Romain Noël, Amélie Goudet, Karen Hinsinger, Aurélien Michau, Valérie Pons, Hajer Abdelkafi, Thomas Secher, Ayaka Shima, Olena Shtanko, Yasuteru Sakurai, Sandrine Cojean, Sébastien Pomel, Vanessa Liévin-Le Moal, Véronique Leignel, Jo-Ana Herweg, Annette Fischer, Ludger Johannes, Kate Harrison, Philippa M Beard, Pascal Clayette, Roger Le Grand, Jonathan O Rayner, Thomas Rudel, Joël Vacus, Philippe M Loiseau, Robert A Davey, Eric Oswald, Jean-Christophe Cintrat, Julien Barbier, Daniel Gillet
Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses. Moreover, Retro-2 is an inhibitor of retrograde transport that affects syntaxin-5-dependent toxins and pathogens...
October 3, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27709137/recent-trends-on-hydrogel-based-drug-delivery-systems-for-infectious-diseases
#20
Arti Vashist, Ajeet Kaushik, Atul Vashist, Rahul Dev Jayant, Asahi Tomitaka, Sharif Ahmad, Y K Gupta, Madhavan Nair
Since centuries, the rapid spread and cure of infectious diseases have been a major concern to the progress and survival of humans. These diseases are a global burden and the prominent cause for worldwide deaths and disabilities. Nanomedicine has emerged as the most excellent tool to eradicate and halt their spread. Various nanoformulations (NFs) using advanced nanotechnology are in demand. Recently, hydrogel and nanogel based drug delivery devices have posed new prospects to simulate the natural intelligence of various biological systems...
October 18, 2016: Biomaterials Science
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