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Ebola drugs

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
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
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
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
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
(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
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
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
Maru Aregawi, Samuel J Smith, Musa Sillah-Kanu, John Seppeh, Anitta R Y Kamara, Ryan O Williams, John J Aponte, Andrea Bosman, Pedro Alonso
BACKGROUND: As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate-amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014-January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres...
2016: Malaria Journal
Baptiste Martin, Thomas Hoenen, Bruno Canard, Etienne Decroly
This review focuses on the recent progress in our understanding of filovirus protein structure/function and its impact on antiviral research. Here we focus on the surface glycoprotein GP1,2 and its different roles in filovirus entry. We first describe the latest advances on the characterization of GP gene-overlapping proteins sGP, ssGP and Δ-peptide. Then, we compare filovirus surface GP1,2 proteins in terms of structure, synthesis and function. As they bear potential in drug-design, the discovery of small organic compounds inhibiting filovirus entry is a currently very active field...
September 14, 2016: Antiviral Research
Marissa Balmith, Mbuso Faya, Mahmoud E S Soliman
The Ebola virus (EboV), formally known as the Ebola hemorrhagic fever (EHF) is an acute viral syndrome causing sporadic outbreaks that have ravaged West Africa. Due to its extreme virulence and highly transmissible nature, Ebola has been classified as a category A bioweapon organism. Only recently have vaccine or drug regimens for the EboV been developed, including Zmapp and peptides. In addition existing drugs which have been repurposed towards anti-EboV activity have been re-examined and are seen to be promising candidates towards combating Ebola...
September 17, 2016: Chemical Biology & Drug Design
Feixiong Cheng, James L Murray, Junfei Zhao, Jinsong Sheng, Zhongming Zhao, Donald H Rubin
Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins...
September 2016: PLoS Computational Biology
Alexandra Greenberg, Rachel Kiddell-Monroe
In recent years, the world has witnessed the tragic outcomes of multiple global health crises. From Ebola to high prices to antibiotic resistance, these events highlight the fundamental constraints of the current biomedical research and development (R&D) system in responding to patient needs globally.To mitigate this lack of responsiveness, over 100 self-identified "alternative" R&D initiatives, have emerged in the past 15 years. To begin to make sense of this panoply of initiatives working to overcome the constraints of the current system, UAEM began an extensive, though not comprehensive, mapping of the alternative biomedical R&D landscape...
2016: Globalization and Health
Robert W Cross, Matthew L Boisen, Molly M Millett, Diana S Nelson, Darin Oottamasathien, Jessica N Hartnett, Abigal B Jones, Augustine Goba, Mambu Momoh, Mohamed Fullah, Zachary A Bornholdt, Marnie L Fusco, Dafna M Abelson, Shunichiro Oda, Bethany L Brown, Ha Pham, Megan M Rowland, Krystle N Agans, Joan B Geisbert, Megan L Heinrich, Peter C Kulakosky, Jeffrey G Shaffer, John S Schieffelin, Brima Kargbo, Momoh Gbetuwa, Sahr M Gevao, Russell B Wilson, Erica Ollmann Saphire, Kelly R Pitts, Sheik Humarr Khan, Donald S Grant, Thomas W Geisbert, Luis M Branco, Robert F Garry
BACKGROUND:  Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. METHODS:  Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development...
October 15, 2016: Journal of Infectious Diseases
Lisa Henß, Simon Beck, Tatjana Weidner, Nadine Biedenkopf, Katja Sliva, Christopher Weber, Stephan Becker, Barbara S Schnierle
BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths...
August 31, 2016: Virology Journal
Anna Kuehne, Amanda Tiffany, Estrella Lasry, Michel Janssens, Clement Besse, Chibuzo Okonta, Kwabena Larbi, Alfred C Pah, Kostas Danis, Klaudia Porten
BACKGROUND: In October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF) implemented a mass drug administration (MDA) of malaria chemoprevention (CP) in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness. METHODS: MSF carried out two rounds of MDA with artesunate/amodiaquine (ASAQ) targeting four neighbourhoods of Monrovia (October to December 2014)...
2016: PloS One
Rachel Fearns, Jerome Deval
Worldwide, respiratory syncytial virus (RSV) causes severe disease in infants, the elderly, and immunocompromised people. No vaccine or effective antiviral treatment is available. RSV is a member of the non-segmented, negative-strand (NNS) group of RNA viruses and relies on its RNA-dependent RNA polymerase to transcribe and replicate its genome. Because of its essential nature and unique properties, the RSV polymerase has proven to be a good target for antiviral drugs, with one compound, ALS-8176, having already achieved clinical proof-of-concept efficacy in a human challenge study...
October 2016: Antiviral Research
Chaturaka Rodrigo, Auda A Eltahla, Rowena A Bull, Jason Grebely, Gregory J Dore, Tanya Applegate, Kimberly Page, Julie Bruneau, Meghan D Morris, Andrea L Cox, William Osburn, Arthur Y Kim, Janke Schinkel, Naglaa H Shoukry, Georg M Lauer, Lisa Maher, Margaret Hellard, Maria Prins, Chris Estes, Homie Razavi, Andrew R Lloyd, Fabio Luciani
BACKGROUND:  Bayesian evolutionary analysis (coalescent analysis) based on genetic sequences has been used to describe the origins and spread of rapidly mutating RNA viruses such as Influenza, Ebola, HIV and hepatitis C virus (HCV). METHODS:  Full length subtype 1a and 3a sequences from early HCV infections from the International Collaborative of Incident HIV and Hepatitis C in Injecting Cohorts (InC3), as well as from public databases from a time window of 1977 - 2012, were used in a coalescent analysis with BEAST software to estimate the origin and progression of the HCV epidemic in Australia and North America...
August 28, 2016: Journal of Infectious Diseases
Chang-Qing Bai, Jin-Song Mu, David Kargbo, Ya-Bin Song, Wen-Kai Niu, Wei-Min Nie, Alex Kanu, Wei-Wei Liu, Yao-Ping Wang, Foday Dafae, Tao Yan, Yi Hu, Yong-Qiang Deng, Hui-Jun Lu, Fan Yang, Xiao-Guang Zhang, Yang Sun, Yu-Xi Cao, Hao-Xiang Su, Yu Sun, Wen-Sen Liu, Cheng-Yu Wang, Jun Qian, Liu Liu, Hong Wang, Yi-Gang Tong, Ze-Yuan Liu, Yun-Song Chen, Hong-Quan Wang, Brima Kargbo, George F Gao, Jia-Fu Jiang
BACKGROUND:  During 2014-2015, an outbreak of Ebola virus disease (EVD) swept across parts of West Africa. No approved antiviral drugs are available for Ebola treatment currently. METHODS:  A retrospective clinical case series was performed for EVD patients in Sierra Leone-China Friendship Hospital. Patients with confirmed EVD were sequentially enrolled and treated with either World Health Organization (WHO)-recommended supportive therapy (control group) from 10 to 30 October, or treated with WHO-recommended therapy plus favipiravir (T-705) from 1 to 10 November 2014...
August 23, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Bryan C Mounce, Teresa Cesaro, Gonzalo Moratorio, Peter Jan Hooikaas, Anna Yakovleva, Scott W Werneke, Everett Clinton Smith, Enzo Z Poirier, Etienne Simon-Loriere, Matthieu Prot, Carole Tamietti, Sandrine Vitry, Romain Volle, Cécile Khou, Marie-Pascale Frenkiel, Anavaj Sakuntabhai, Francis Delpeyroux, Nathalie Pardigon, Marie Flamand, Giovanna Barba-Spaeth, Monique Lafon, Mark R Denison, Matthew L Albert, Marco Vignuzzi
: RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among the human population, and their ability to evolve resistance to antiviral therapies. The recent emergence of chikungunya virus, Zika virus, and Ebola virus highlights the struggles to contain outbreaks. A significant hurdle is the availability of antivirals to treat the infected or protect at-risk populations. While several compounds show promise in vitro and in vivo, these outbreaks underscore the need to accelerate drug discovery...
November 1, 2016: Journal of Virology
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