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https://www.readbyqxmd.com/read/29305306/filovirus-proteins-for-antiviral-drug-discovery-structure-function-of-proteins-involved-in-assembly-and-budding
#1
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/29299527/a-single-amino-acid-change-in-the-marburg-virus-glycoprotein-arises-during-serial-cell-culture-passages-and-attenuates-the-virus-in-a-macaque-model-of-disease
#2
Kendra J Alfson, Laura E Avena, Jenny Delgado, Michael W Beadles, Jean L Patterson, Ricardo Carrion, Anthony Griffiths
Marburg virus (MARV) causes disease with high case fatality rates, and there are no approved vaccines or therapies. Licensing of MARV countermeasures will likely require approval via the FDA's Animal Efficacy Rule, which requires well-characterized animal models that recapitulate human disease. This includes selection of the virus used for exposure and ensuring that it retains the properties of the original isolate. The consequences of amplification of MARV for challenge studies are unknown. Here, we serially passaged and characterized MARV through 13 passes from the original isolate...
January 2018: MSphere
https://www.readbyqxmd.com/read/29289666/efficacy-of-favipiravir-t-705-in-nonhuman-primates-infected-with-ebola-virus-or-marburg-virus
#3
Sandra L Bixler, Thomas M Bocan, Jay Wells, Kelly Wetzel, Sean Van Tongeren, Lian Dong, Nicole Lackemeyer, Ginger Donnelly, Lisa Cazares, Jonathan Nuss, Veronica Soloveva, Keith Koistinen, Lisa Welch, Carol Epstein, Li-Fang Liang, Dennis Giesing, Robert Lenk, Sina Bavari, Travis K Warren
Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA...
December 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29289664/intracellular-conversion-and-in-vivo-dose-response-of-favipiravir-t-705-in-rodents-infected-with-ebola-virus
#4
Sandra L Bixler, Thomas M Bocan, Jay Wells, Kelly Wetzel, Sean Van Tongeren, Nicole Lackemeyer, Ginger Donnelly, Lisa Cazares, Veronica Soloveva, Lisa Welch, Carol Epstein, Li-Fang Liang, Dennis Giesing, Robert Lenk, Sina Bavari, Travis K Warren
During the 2013-2016 Ebola virus (EBOV) outbreak in West Africa, our team at USAMRIID evaluated the antiviral activity of a number of compounds, including favipiravir (T-705), in vitro and in mouse and nonhuman primate (NHP) models of Ebola virus disease. In this short communication, we present our findings for favipiravir in cell culture and in mice, while an accompanying paper presents the results of NHP studies. We confirmed previous reports that favipiravir has anti-EBOV activity in mice. Additionally, we found that the active form of favipiravir is generated in mice in tissues relevant for the pathogenesis of EBOV infection...
December 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29227420/us-state-public-health-departments-special-pathogen-planning
#5
Jocelyn J Herstein, Paul D Biddinger, Shawn G Gibbs, Aurora B Le, Katelyn C Jelden, Angela L Hewlett, John J Lowe
CONTEXT: US state public health departments played key roles in planning for and responding to confirmed and suspected cases of Ebola virus disease (EVD) during the 2014-2016 outbreak, including designating select hospitals as high-level isolation units (HLIUs) for EVD treatment in conjunction with the Centers for Disease Control and Prevention. OBJECTIVE: To identify existing guidelines and perspectives of state health departments pertaining to the management and transport of patients with EVD and other highly hazardous communicable diseases (HHCDs)...
December 7, 2017: Journal of Public Health Management and Practice: JPHMP
https://www.readbyqxmd.com/read/29175127/retro-2-and-its-dihydroquinazolinone-derivatives-inhibit-filovirus-infection
#6
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/29153506/role-of-non-local-interactions-between-cdr-loops-in-binding-affinity-of-mr78-antibody-to-marburg-virus-glycoprotein
#7
Amandeep K Sangha, Jinhui Dong, Lauren Williamson, Takao Hashiguchi, Erica Ollmann Saphire, James E Crowe, Jens Meiler
An atomic-detail model of the Marburg virus glycoprotein in complex with a neutralizing human monoclonal antibody designated MR78 was constructed using Phenix.Rosetta starting from a 3.6Å crystallographic density map. The Asp at T6 in the HCDR3's bulged torso cannot form the canonical salt bridge as position T2 lacks an Arg or Lys residue. It instead engages in a hydrogen bond interaction with a Tyr contributed by the HCDR1 loop. This inter-CDR loop interaction stabilizes the bulged conformation needed for binding to the viral glycoprotein: a Tyr to Phe mutant displays a binding affinity reduced by a factor of at least 10...
November 14, 2017: Structure
https://www.readbyqxmd.com/read/29144446/structure-and-assembly-of-the-ebola-virus-nucleocapsid
#8
William Wan, Larissa Kolesnikova, Mairi Clarke, Alexander Koehler, Takeshi Noda, Stephan Becker, John A G Briggs
Ebola and Marburg viruses are filoviruses: filamentous, enveloped viruses that cause haemorrhagic fever. Filoviruses are within the order Mononegavirales, which also includes rabies virus, measles virus, and respiratory syncytial virus. Mononegaviruses have non-segmented, single-stranded negative-sense RNA genomes that are encapsidated by nucleoprotein and other viral proteins to form a helical nucleocapsid. The nucleocapsid acts as a scaffold for virus assembly and as a template for genome transcription and replication...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29142131/single-dose-trivalent-vesiculovax-vaccine-protects-macaques-from-lethal-ebolavirus-and-marburgvirus-challenge
#9
Demetrius Matassov, Chad E Mire, Theresa Latham, Joan B Geisbert, Rong Xu, Ayuko Ota-Setlik, Krystle N Agans, Dean J Kobs, Morgan Q S Wendling, Amanda Burnaugh, Thomas L Rudge, Carol L Sabourin, Michael A Egan, David K Clarke, Thomas W Geisbert, John H Eldridge
Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV, Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29106386/sirna-rescues-nonhuman-primates-from-advanced-marburg-and-ravn-virus-disease
#10
Emily P Thi, Chad E Mire, Amy Ch Lee, Joan B Geisbert, Raul Ursic-Bedoya, Krystle N Agans, Marjorie Robbins, Daniel J Deer, Robert W Cross, Andrew S Kondratowicz, Karla A Fenton, Ian MacLachlan, Thomas W Geisbert
Ebolaviruses and marburgviruses belong to the family Filoviridae and cause high lethality in infected patients. There are currently no licensed filovirus vaccines or antiviral therapies. The development of broad-spectrum therapies against members of the Marburgvirus genus, including Marburg virus (MARV) and Ravn virus (RAVV), is difficult because of substantial sequence variability. RNAi therapeutics offer a potential solution, as identification of conserved target nucleotide sequences may confer activity across marburgvirus variants...
November 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29070075/marburg-virus-like-particles-by-co-expression-of-glycoprotein-and-matrix-protein-in-insect-cells-induces-immune-responses-in-mice
#11
Weiwei Gai, Xuexing Zheng, Chong Wang, Hualei Wang, Yongkun Zhao, Qi Wang, Gary Wong, Weijiao Zhang, Na Feng, Boning Qiu, Hang Chi, Nan Li, Tiecheng Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
BACKGROUND: Marburg virus (MARV) causes severe haemorrhagic fever in humans and nonhuman primates and has a high mortality rate. However, effective drugs or licensed vaccines are not currently available to control the outbreak and spread of this disease. METHODS: In this study, we generated MARV virus-like particles (VLPs) by co-expressing the glycoprotein (GP) and matrix protein (VP40) using the baculovirus expression system. MARV VLPs and three adjuvants, Poria cocos polysaccharide (PCP-II), poly(I:C) and aluminium hydroxide, were evaluated after intramuscular vaccination in mice...
October 25, 2017: Virology Journal
https://www.readbyqxmd.com/read/29038656/unveiling-a-drift-resistant-cryptotope-within-marburgvirus-nucleoprotein-recognized-by-llama-single-domain-antibodies
#12
John Anthony Garza, Alexander Bryan Taylor, Laura Jo Sherwood, Peter John Hart, Andrew Hayhurst
Marburg virus (MARV) is a highly lethal hemorrhagic fever virus that is increasingly re-emerging in Africa, has been imported to both Europe and the US, and is also a Tier 1 bioterror threat. As a negative sense RNA virus, MARV has error prone replication which can yield progeny capable of evading countermeasures. To evaluate this vulnerability, we sought to determine the epitopes of 4 llama single-domain antibodies (sdAbs or VHH) specific for nucleoprotein (NP), each capable of forming MARV monoclonal affinity reagent sandwich assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29034123/ecological-niche-modeling-for-filoviruses-a-risk-map-for-ebola-and-marburg-virus-disease-outbreaks-in-uganda
#13
Luke Nyakarahuka, Samuel Ayebare, Gladys Mosomtai, Clovice Kankya, Julius Lutwama, Frank Norbert Mwiine, Eystein Skjerve
INTRODUCTION: Uganda has reported eight outbreaks caused by filoviruses between 2000 to 2016, more than any other country in the world. We used species distribution modeling to predict where filovirus outbreaks are likely to occur in Uganda to help in epidemic preparedness and surveillance. METHODS: The MaxEnt software, a machine learning modeling approach that uses presence-only data was used to establish filovirus - environmental relationships. Presence-only data for filovirus outbreaks were collected from the field and online sources...
September 5, 2017: PLoS Currents
https://www.readbyqxmd.com/read/29031848/local-national-and-regional-viral-haemorrhagic-fever-pandemic-potential-in-africa-a-multistage-analysis
#14
David M Pigott, Aniruddha Deshpande, Ian Letourneau, Chloe Morozoff, Robert C Reiner, Moritz U G Kraemer, Shannon E Brent, Isaac I Bogoch, Kamran Khan, Molly H Biehl, Roy Burstein, Lucas Earl, Nancy Fullman, Jane P Messina, Adrian Q N Mylne, Catherine L Moyes, Freya M Shearer, Samir Bhatt, Oliver J Brady, Peter W Gething, Daniel J Weiss, Andrew J Tatem, Luke Caley, Tom De Groeve, Luca Vernaccini, Nick Golding, Peter Horby, Jens H Kuhn, Sandra J Laney, Edmond Ng, Peter Piot, Osman Sankoh, Christopher J L Murray, Simon I Hay
BACKGROUND: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean-Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease...
December 16, 2017: Lancet
https://www.readbyqxmd.com/read/28945945/macromolecular-antiviral-agents-against-zika-ebola-sars-and-other-pathogenic-viruses
#15
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/28892520/knowledge-and-attitude-towards-ebola-and-marburg-virus-diseases-in-uganda-using-quantitative-and-participatory-epidemiology-techniques
#16
Luke Nyakarahuka, Eystein Skjerve, Daisy Nabadda, Doreen Chilolo Sitali, Chisoni Mumba, Frank N Mwiine, Julius J Lutwama, Stephen Balinandi, Trevor Shoemaker, Clovice Kankya
BACKGROUND: Uganda has reported five (5) Ebola virus disease outbreaks and three (3) Marburg virus disease outbreaks from 2000 to 2016. Peoples' knowledge and attitude towards Ebola and Marburg virus disease impact on control and prevention measures especially during outbreaks. We describe knowledge and attitude towards Ebola and Marburg virus outbreaks in two affected communities in Uganda to inform future outbreak responses and help in the design of health education and communication messages...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28821722/egyptian-rousette-bats-maintain-long-term-protective-immunity-against-marburg-virus-infection-despite-diminished-antibody-levels
#17
Amy J Schuh, Brian R Amman, Tara K Sealy, Jessica R Spengler, Stuart T Nichol, Jonathan S Towner
Although bats are natural reservoir hosts for numerous zoonotic viruses, little is known about the long-term dynamics of the host immune response following infection and how these viruses are maintained in nature. The Egyptian rousette bat (ERB) is a known reservoir host for Marburg virus (MARV). Following infection of ERBs with MARV, virus-specific IgG antibodies are induced but rapidly wane and by 3 months post-infection the bats are seronegative. To determine whether reinfection of ERBs plays a role in MARV maintenance, we challenge groups of ERBs that were "naturally" or experimentally infected with MARV 17-24 months prior...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28766193/filovirus-research-how-it-began
#18
Werner Slenczka
The first reported filovirus outbreak occurred in August 1967, when laboratory workers in Marburg and Frankfurt, Germany, and Belgrade, Yugoslavia (now Serbia) became infected with an unknown highly pathogenic agent. The disease was characterized by high fever, malaise, rash, hemorrhagic and tetanic manifestations, and high lethality, amounting to 25%. The disease was introduced to Europe by grivets (Chlorocebus aethiops), which were used for biomedical research and vaccine production. The causative agent, Marburg virus, was isolated and identified by scientists of the University of Marburg, Germany in cooperation with specialists for viral electron microscopy at the Bernhard Nocht Institute in Hamburg, Germany...
August 2, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28750668/from-hybridomas-to-a-robust-microalgal-based-production-platform-molecular-design-of-a-diatom-secreting-monoclonal-antibodies-directed-against-the-marburg-virus-nucleoprotein
#19
Franziska Hempel, Michael Maurer, Björn Brockmann, Christian Mayer, Nadine Biedenkopf, Anne Kelterbaum, Stephan Becker, Uwe G Maier
BACKGROUND: The ideal protein expression system should provide recombinant proteins in high quality and quantity involving low production costs only. However, especially for complex therapeutic proteins like monoclonal antibodies many challenges remain to meet this goal and up to now production of monoclonal antibodies is very costly and delicate. Particularly, emerging disease outbreaks like Ebola virus in Western Africa in 2014-2016 make it necessary to reevaluate existing production platforms and develop robust and cheap alternatives that are easy to handle...
July 27, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#20
Spencer W Stonier, Andrew S Herbert, Ana I Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V Abramovitch Dahan, Rebekah M James, Moses Egesa, Stephen Cose, Julius Julian Lutwama, Leslie Lobel, John M Dye
Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized...
September 4, 2017: Journal of Experimental Medicine
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