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Ebola drugs

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https://www.readbyqxmd.com/read/29452047/lessons-learned-from-ebola-vaccine-r-d-during-a-public-health-emergency
#1
Marie-Paule Kieny
In spite of a complete lack of Research and Development (R&D) preparedness, the 2013-2016 West-Africa Ebola experience demonstrated that it is possible to compress R&D timelines to less than a single year, from a more usual decade or longer. This is mostly to be credited to an unprecedented collaborative effort building on the availability of a small number of candidate diagnostic tests, drugs and vaccines that could be moved rapidly into the clinical phase evaluation. The World Health Organization (WHO) led international consultations and activities - including the organization of a successful Ebola vaccine efficacy trial in Guinea - as a contribution to the unprecedented global efforts to control the Ebola epidemic...
February 16, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29428508/the-molecular-tweezer-clr01-inhibits-ebola-and-zika-virus-infection
#2
Annika E Röcker, Janis A Müller, Erik Dietzel, Mirja Harms, Franziska Krüger, Christian Heid, Andrea Sowislok, Camilla Frich Riber, Alexandra Kupke, Sina Lippold, Jens von Einem, Judith Beer, Bernd Knöll, Stephan Becker, Jonas Schmidt-Chanasit, Markus Otto, Olli Vapalahti, Alexander N Zelikin, Gal Bitan, Thomas Schrader, Jan Münch
Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule previously has been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner...
February 8, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29369776/successful-treatment-of-marburg-virus-with-orally-administrated-t-705-favipiravir-in-a-mouse-model
#3
Wenjun Zhu, Zirui Zhang, Shihua He, Gary Wong, Logan Banadyga, Xiangguo Qiu
Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola)...
January 21, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29361403/structure-based-virtual-screening-of-the-ebola-virus-trimeric-glycoprotein-using-consensus-scoring
#4
Abdulmujeeb T Onawole, Temitope U Kolapo, Kazeem O Sulaiman, Rukayat O Adegoke
Ebola virus (EBOV) causes zoonotic viral infection with a potential risk of global spread and a highly fatal effect on humans. Till date, no drug has gotten market approval for the treatment of Ebola virus disease (EVD), and this perhaps allows the use of both experimental and computational approaches in the antiviral drug discovery process. The main target of potential vaccines that are recently undergoing clinical trials is trimeric glycoprotein (GP) of the EBOV and its exact crystal structure was used in this structure based virtual screening study, with the aid of consensus scoring to select three possible hit compounds from about 36 million compounds in MCULE's database...
November 22, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29305306/filovirus-proteins-for-antiviral-drug-discovery-structure-function-of-proteins-involved-in-assembly-and-budding
#5
REVIEW
Baptiste Martin, Olivier Reynard, Viktor Volchkov, Etienne Decroly
There are no approved medications for the treatment of Marburg or Ebola virus infection. In two previous articles (Martin et al., 2016, Martin et al., 2017), we reviewed surface glycoprotein and replication proteins structure/function relationship to decipher the molecular mechanisms of filovirus life cycle and identify antiviral strategies. In the present article, we recapitulate knowledge about the viral proteins involved in filovirus assembly and budding. First we describe the structural data available for viral proteins associated with virus assembly and virion egress and then, we integrate the structural features of these proteins in the functional context of the viral replication cycle...
January 2, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29297408/nubia-s-mother-being-pregnant-in-the-time-of-experimental-vaccines-and-therapeutics-for-ebola
#6
Séverine Caluwaerts
During the 2014-2016 Ebola epidemic, Médecins Sans Frontières (MSF) treated Ebola-positive pregnant women in its Ebola Treatment Centers (ETCs). For pregnant women with confirmed Ebola virus disease, inclusion in clinical vaccine/drug/therapeutic trials was complicated. Despite their extremely high Ebola-related mortality in previous epidemics (89-93%) and a neonatal mortality of 100%, theoretical concerns about safety of vaccines and therapeutics in pregnancy were invoked, limiting pregnant women's access to an experimental live attenuated vaccine and brincidofovir, an experimental antiviral...
December 14, 2017: Reproductive Health
https://www.readbyqxmd.com/read/29297366/protected-to-death-systematic-exclusion-of-pregnant-women-from-ebola-virus-disease-trials
#7
Melba F Gomes, Vânia de la Fuente-Núñez, Abha Saxena, Annette C Kuesel
BACKGROUND: For 30 years, women have sought equal opportunity to be included in trials so that drugs are equitably studied in women as well as men; regulatory guidelines have changed accordingly. Pregnant women, however, continue to be excluded from trials for non-obstetric conditions, though they have been included for trials of life-threatening diseases because prospects for maternal survival outweighed potential fetal risks. Ebola virus disease is a life-threatening infection without approved treatments or vaccines...
December 14, 2017: Reproductive Health
https://www.readbyqxmd.com/read/29236288/disaster-preparedness-biological-threats-and-treatment-options
#8
Navaneeth Narayanan, Clifton R Lacy, Joseph E Cruz, Meghan Nahass, Jonathan Karp, Joseph A Barone, Evelyn Hermes-DeSantis
Biological disasters can be natural, accidental, or intentional. Biological threats have made a lasting impact on civilization. This review will focus on agents of clinical significance, bioterrorism, and national security; specifically Category A agents (anthrax, botulism, plague, tularemia, and smallpox), as well as briefly discuss other naturally-emerging infections of public health significance including Ebola virus (also a Category A agent) and Zika virus. The role of the pharmacist in disaster preparedness and disaster response is multifaceted and important...
December 13, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29212933/characterization-of-an-influenza-virus-pseudotyped-with-ebolavirus-glycoprotein
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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