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https://www.readbyqxmd.com/read/29212933/characterization-of-an-influenza-virus-pseudotyped-with-ebolavirus-glycoprotein
#1
Julie Xiao, Pramila Rijal, Lisa Schimanski, Arun Kumar Tharkeshwar, Edward Wright, Wim Annaert, Alain Townsend
We have produced a new Ebola virus pseudotype: E-S-FLU, which can be handled in biosafety level-1/2 containment for laboratory analysis. E-S-FLU is a single cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza haemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU production. Infection of cells by E-S-FLU was dependent on Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29175127/retro-2-and-its-dihydroquinazolinone-derivatives-inhibit-filovirus-infection
#2
Olena Shtanko, Yasuteru Sakurai, Ann N Reyes, Romain Noël, Jean-Christophe Cintrat, Daniel Gillet, Julien Barbier, Robert A Davey
Members of the family Filoviridae cause severe, often fatal disease in humans, for which there are no approved vaccines and only a few experimental drugs tested in animal models. Retro-2, a small molecule that inhibits retrograde trafficking of bacterial and plant toxins inside host cells, has been demonstrated to be effective against a range of bacterial and virus pathogens, both in vitro and in animal models. Here, we demonstrated that Retro-2 and its derivatives, Retro-2.1 and compound 25, blocked infection by Ebola virus and Marburg virus in vitro...
November 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29163402/pharmacological-induction-of-heme-oxygenase-1-impairs-nuclear-accumulation-of-herpes-simplex-virus-capsids-upon-infection
#3
Francisco J Ibáñez, Mónica A Farías, Angello Retamal-Díaz, Janyra A Espinoza, Alexis M Kalergis, Pablo A González
Heme oxygenase-1 (HO-1) is an inducible enzyme that is expressed in response to physical and chemical stresses, such as ultraviolet radiation, hyperthermia, hypoxia, reactive oxygen species (ROS), as well as cytokines, among others. Its activity can be positively modulated by cobalt protoporphyrin (CoPP) and negatively by tin protoporphirin (SnPP). Once induced, HO-1 degrades iron-containing heme into ferrous iron (Fe(2+)), carbon monoxide (CO) and biliverdin. Importantly, numerous products of HO-1 are cytoprotective with anti-apoptotic, anti-oxidant, anti-inflammatory, and anti-cancer effects...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29133569/efficacy-of-tilorone-dihydrochloride-against-ebola-virus-infection
#4
Sean Ekins, Mary A Lingerfelt, Jason E Comer, Alexander N Freiberg, Jon C Mirsalis, Kathleen O'Loughlin, Anush Harutyunyan, Claire McFarlane, Carol E Green, Peter B Madrid
Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside of the US. A machine learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9 and 1A2)...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29116351/continuous-flow-microfluidic-qrt-pcr-system-for-rna-virus-detection
#5
B Leticia Fernández-Carballo, Christine McBeth, Ian McGuiness, Maxim Kalashnikov, Christoph Baum, Salvador Borrós, Andre Sharon, Alexis F Sauer-Budge
One of the main challenges in the diagnosis of infectious diseases is the need for rapid and accurate detection of the causative pathogen in any setting. Rapid diagnosis is key to avoiding the spread of the disease, to allow proper clinical decisions to be made in terms of patient treatment, and to mitigate the rise of drug-resistant pathogens. In the last decade, significant interest has been devoted to the development of point-of-care reverse transcription polymerase chain reaction (PCR) platforms for the detection of RNA-based viral pathogens...
November 7, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29058516/clinician-initiated-research-on-treating-the-host-response-to-pandemic-influenza
#6
David S Fedson
To prepare for the next influenza pandemic and other emerging virus diseases, scientists and health officials are focused on developing new vaccines and treatments that target these viruses. Ideally, these interventions could be highly effective, but for many practical reasons these "top down" efforts are unlikely to provide clinicians with what they will need to manage their patients. As a "bottom up" alternative, combinations of generic drugs like statins and angiotensin receptor blockers (ARBs) might be used to treat the host response to infection...
October 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29053626/a-systematic-review-of-computational-drug-discovery-development-and-repurposing-for-ebola-virus-disease-treatment
#7
REVIEW
James Schuler, Matthew L Hudson, Diane Schwartz, Ram Samudrala
Ebola virus disease (EVD) is a deadly global public health threat, with no currently approved treatments. Traditional drug discovery and development is too expensive and inefficient to react quickly to the threat. We review published research studies that utilize computational approaches to find or develop drugs that target the Ebola virus and synthesize its results. A variety of hypothesized and/or novel treatments are reported to have potential anti-Ebola activity. Approaches that utilize multi-targeting/polypharmacology have the most promise in treating EVD...
October 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29047180/systematic-screening-of-viral-entry-inhibitors-using-surface-plasmon-resonance
#8
REVIEW
Penmetcha K R Kumar
Viral binding and entry into host cells for various viruses have been studied extensively, yielding a detailed understanding of the overall viral entry process. As cell entry is an essential and requisite process by which a virus initiates infection, it is an attractive target for therapeutic intervention. The advantages of targeting viral entry are an extracellular target site, relatively easy access for biological interventions, and lower toxicity. Several cell-based strategies and biophysical techniques have been used to screen compounds that block viral entry...
October 18, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29028879/review-of-computational-methods-for-virus-host-protein-interaction-prediction-a-case-study-on-novel-ebola-human-interactions
#9
Anup Kumar Halder, Pritha Dutta, Mahantapas Kundu, Subhadip Basu, Mita Nasipuri
Identification of potential virus-host interactions is useful and vital to control the highly infectious virus-caused diseases. This may contribute toward development of new drugs to treat the viral infections. Recently, database records of clinically and experimentally validated interactions between a small set of human proteins and Ebola virus (EBOV) have been published. Using the information of the known human interaction partners of EBOV, our main objective is to identify a set of proteins that may interact with EBOV proteins...
September 26, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/28994386/-integrating-clinical-research-into-epidemic-response-the-field-perspective-in-the-ebola-experience
#10
Denis Malvy, Daouda Sissoko, Alseny-Modet Camara
During the 2013-2016 west African Ebola outbreak that affected West Africa, accelerated clinical trials, testing unproven but promising and potentially lifesaving experimental interventions emerged as a key component of the global outbreak. In 2017, no Ebola medical countermeasures had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried a list of potential drug candidates developed or repurposed with demonstrated antiviral efficacy in vitro or in animal models...
October 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28968729/a-survey-on-ebola-genome-and-current-trends-in-computational-research-on-the-ebola-virus
#11
Pritha Dutta, Anup Kumar Halder, Subhadip Basu, Mahantapas Kundu
A detailed understanding of the Ebola virus (EBOV) pathogenesis has not been possible because of safety concerns, which arise while handling the live EBOV. Understanding the mechanisms involved in EBOV entry, replication and inhibition of the antiviral response in the host cell are crucial for the development of effective therapeutic measures. In this article, we provide a description of the EBOV genome and the role of each EBOV protein in spreading infection in the host cell. We also discuss some of the major computational works done on EBOV for the purpose of developing effective vaccines and drugs...
August 29, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/28945945/macromolecular-antiviral-agents-against-zika-ebola-sars-and-other-pathogenic-viruses
#12
Franziska Schandock, Camilla Frich Riber, Annika Röcker, Janis A Müller, Mirja Harms, Paulina Gajda, Kaja Zuwala, Anna H F Andersen, Kaja Borup Løvschall, Martin Tolstrup, Florian Kreppel, Jan Münch, Alexander N Zelikin
Viral pathogens continue to constitute a heavy burden on healthcare and socioeconomic systems. Efforts to create antiviral drugs repeatedly lag behind the advent of pathogens and growing understanding is that broad-spectrum antiviral agents will make strongest impact in future antiviral efforts. This work performs selection of synthetic polymers as novel broadly active agents and demonstrates activity of these polymers against Zika, Ebola, Lassa, Lyssa, Rabies, Marburg, Ebola, influenza, herpes simplex, and human immunodeficiency viruses...
September 25, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28930583/ibuprofen-as-a-template-molecule-for-drug-design-against-ebola-virus
#13
Slobodan Paessler, Cheng Huang, Milan Sencanski, Nevena Veljkovic, Vladimir Perovic, Sanja Glisic, Veljjko Veljkovic
The Ebola virus outbreak in West Africa 2015 and Congo 2017, point out an urgent need for development of drugs against this important pathogen. Previously, by repurposing virtual screening of 6438 drugs from DrugBank, ibuprofen was selected as a possible inhibitor of the Ebola virus infection. The results of an additional docking analysis as well as experimental results showing measurable anti-Ebola effect of ibuprofen in cell culture suggest ibuprofen as a promising molecular template for the development of drugs for treatment of the infection by Ebola virus...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28917841/graphene-vp40-interactions-and-potential-disruption-of-the-ebola-virus-matrix-filaments
#14
Jeevan B Gc, Rudramani Pokhrel, Nisha Bhattarai, Kristen A Johnson, Bernard S Gerstman, Robert V Stahelin, Prem P Chapagain
Ebola virus infections cause hemorrhagic fever that often results in very high fatality rates. In addition to exploring vaccines, development of drugs is also essential for treating the disease and preventing the spread of the infection. The Ebola virus matrix protein VP40 exists in various conformational and oligomeric forms and is a potential pharmacological target for disrupting the virus life-cycle. Here we explored graphene-VP40 interactions using molecular dynamics simulations and graphene pelleting assays...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28890666/discovering-drugs-for-the-treatment-of-ebola-virus
#15
REVIEW
Sandra L Bixler, Allen J Duplantier, Sina Bavari
PURPOSE OF REVIEW: Ebola virus, a member of the Filoviridae family, is a causative agent of severe viral hemorrhagic fever in humans. Over the past 40 years, the virus has been linked to several high mortality outbreaks in Africa with the recent West African outbreak resulting in over 11,000 deaths. This review provides a summary of the status of the drug discovery and development process for therapeutics for Ebola virus disease, with a focus on the strategies being used and the challenges facing each stage of the process...
2017: Current Treatment Options in Infectious Diseases
https://www.readbyqxmd.com/read/28878087/novel-stable-ebola-virus-minigenome-replicon-reveals-remarkable-stability-of-the-viral-genome
#16
Wanyin Tao, Tianyu Gan, Mingzhe Guo, Yongfen Xu, Jin Zhong
Ebola virus (EBOV) causes severe hemorrhagic fever in humans and other primates with a high case fatality rate. No approved drug or vaccine of EBOV is available, which necessitates better understanding of the virus life cycle. Studies on EBOV have been hampered because experimentations involving live virus are restricted to biosafety level 4 (BSL-4) laboratories. EBOV minigenome system has provided researchers with the opportunity to study EBOV under BSL-2 conditions. Here, we developed a novel EBOV minigenome replicon which, to our knowledge, is the first EBOV cell culture system that can stably replicate and transcribe EBOV minigenome...
September 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28852537/ebola-and-fda-reviewing-the-response-to-the-2014-outbreak-to-find-lessons-for-the-future
#17
Emily A Largent
In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak-as now-there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDA's global role in drug development, approval, and access...
December 2016: Journal of Law and the Biosciences
https://www.readbyqxmd.com/read/28827211/development-and-deployment-of-the-openmrs-ebola-electronic-health-record-system-for-an-ebola-treatment-center-in-sierra-leone
#18
Shefali Oza, Darius Jazayeri, Jonathan M Teich, Ellen Ball, Patricia Alexandra Nankubuge, Job Rwebembera, Kevin Wing, Alieu Amara Sesay, Andrew S Kanter, Glauber D Ramos, David Walton, Rachael Cummings, Francesco Checchi, Hamish S Fraser
BACKGROUND: Stringent infection control requirements at Ebola treatment centers (ETCs), which are specialized facilities for isolating and treating Ebola patients, create substantial challenges for recording and reviewing patient information. During the 2014-2016 West African Ebola epidemic, paper-based data collection systems at ETCs compromised the quality, quantity, and confidentiality of patient data. Electronic health record (EHR) systems have the potential to address such problems, with benefits for patient care, surveillance, and research...
August 21, 2017: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/28822631/clinical-evaluation-of-ebola-virus-disease-therapeutics
#19
REVIEW
Guodong Liu, Gary Wong, Shuo Su, Yuhai Bi, Frank Plummer, George F Gao, Gary Kobinger, Xiangguo Qiu
Ebola virus disease (EVD) was first described over 40 years ago, but no treatment has been approved for humans. The 2013-2016 EVD outbreak in West Africa has expedited the clinical evaluation of several candidate therapeutics that act through different mechanisms, but with mixed results. Nevertheless, these studies are important because the accumulation of clinical data and valuable experience in conducting efficacy trials under emergency circumstances will lead to better implementation of similar studies in the future...
August 16, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28820067/a-comprehensive-review-on-ebola-ebov-virus-future-prospects
#20
Sajad Khan, Muhammad, Abdur Rauf, Ahsan Khan, Muhammad Rizwan, Seema Patel, Haroon Khan, Adel M Mahasneh, Mohammad S Mubarak
Ebola virus (EBOV) was discovered for the first time in 1976. It belongs to the family Filoviridae, which causes hemorrhagic fever that could lead to death in a few days. West Africa faced a major outbreak where symptoms appeared in the form of chills, myalgia, fever, diarrhea, and vomiting, and the disease finally reached a severe state as a result of hemorrhagic complications and failure of multiple organs. EBOV spreads by contact with body fluids of an infected person such as blood, saliva, urine, and seminal fluid, and also spreads by a contact with contaminated surfaces...
August 16, 2017: Infectious Disorders Drug Targets
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