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Marburg virus

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https://www.readbyqxmd.com/read/28645623/identification-of-a-coumarin-based-antihistamine-as-an-anti-filoviral-entry-inhibitor
#1
Han Cheng, Adam Schafer, Veronica Soloveva, Dima Gharaibeh, Tara Kenny, Cary Retterer, Rouzbeh Zamani, Sina Bavari, Norton P Peet, Lijun Rong
Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry...
June 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28636653/the-ebola-virus-vp35-protein-binds-viral-immunostimulatory-and-host-rnas-identified-through-deep-sequencing
#2
Kari A Dilley, Alexander A Voorhies, Priya Luthra, Vinita Puri, Timothy B Stockwell, Hernan Lorenzi, Christopher F Basler, Reed S Shabman
Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA...
2017: PloS One
https://www.readbyqxmd.com/read/28622346/flavivirus-and-filovirus-evoprinters-new-alignment-tools-for-the-comparative-analysis-of-viral-evolution
#3
Thomas Brody, Amarendra S Yavatkar, Dong Sun Park, Alexander Kuzin, Jermaine Ross, Ward F Odenwald
BACKGROUND: Flavivirus and Filovirus infections are serious epidemic threats to human populations. Multi-genome comparative analysis of these evolving pathogens affords a view of their essential, conserved sequence elements as well as progressive evolutionary changes. While phylogenetic analysis has yielded important insights, the growing number of available genomic sequences makes comparisons between hundreds of viral strains challenging. We report here a new approach for the comparative analysis of these hemorrhagic fever viruses that can superimpose an unlimited number of one-on-one alignments to identify important features within genomes of interest...
June 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28611428/deep-sequencing-of-marburg-virus-genome-during-sequential-mouse-passaging-and-cell-culture-adaptation-reveals-extensive-changes-over-time
#4
Haiyan Wei, Jonathan Audet, Gary Wong, Shihua He, Xueyong Huang, Todd Cutts, Steven Theriault, Bianli Xu, Gary Kobinger, Xiangguo Qiu
Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28603449/filoviruses-and-bats
#5
Amy J Schuh, Brian R Amman, Jonathan S Towner
While Reston and Lloviu viruses have never been associated with human disease, the other filoviruses cause outbreaks of hemorrhagic fever characterised by person-to-person transmission and high case fatality ratios. Cumulative evidence suggests that bats are the most likely reservoir hosts of the filoviruses. Ecological investigations following Marburg virus disease outbreaks associated with entry into caves inhabited by Rousettus aegyptiacus bats led to the identification of this bat species as the natural reservoir host of the marburgviruses...
March 2017: Microbiology Australia
https://www.readbyqxmd.com/read/28592526/novel-cross-reactive-monoclonal-antibodies-against-ebolavirus-glycoproteins-show-protection-in-a-murine-challenge-model
#6
Jim Duehr, Teddy John Wohlbold, Lisa Oestereich, Veronika Chromikova, Fatima Amanat, Madhusudan Rajendran, Sergio Gomez-Medina, Ignacio Mena, Benjamin R TenOever, Adolfo García-Sastre, Christopher F Basler, Cesar Munoz-Fontela, Florian Krammer
Out of an estimated 31,100 cases since its discovery in 1976, ebolaviruses have caused approximately 13,000 deaths. The vast majority (∼11,000) of these occurred during the 2013-2016 West African epidemic. Three out of five species in the genus are known to cause Ebola Virus Disease in humans. Several monoclonal antibodies against the ebolavirus glycoprotein are currently in development as therapeutics. However, there is still a paucity of monoclonal antibodies that can cross-react between the glycoproteins of different ebolavirus species and the mechanism of these monoclonal antibody therapeutics are still not understood in detail...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28580138/plasma-membrane-association-facilitates-conformational-changes-in-the-marburg-virus-protein-vp40-dimer
#7
Nisha Bhattarai, Jeevan B Gc, Bernard S Gerstman, Robert V Stahelin, Prem P Chapagain
Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch...
April 26, 2017: RSC Advances
https://www.readbyqxmd.com/read/28573607/marburg-and-ebolaviruses-a-look-back-and-lessons-for-the-future
#8
Hans Dieter Klenk, Werner Slenczka
Since the discovery of Marburg virus 50 years ago, filoviruses have reemerged in the human population more than 40 times. Already the first episode was as dramatic as most of the subsequent ones, but none of them was as devastating as the West-African Ebola virus outbreak in 2013-2015. Although progress toward a better understanding of the viruses is impressive, there is clearly a need to improve and strengthen the measures to detect and control these deadly infections.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28566377/structural-insight-into-nucleoprotein-conformation-change-chaperoned-by-vp35-peptide-in-marburg-virus
#9
Baocheng Liu, Shishang Dong, Guobang Li, Wenming Wang, Xiang Liu, Yantong Wang, Cheng Yang, Zihe Rao, Yu Guo
Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNP undergo a transition from RNA-bound form to template-free form, to open access for the interaction between viral polymerase with RNA template. In filovirus, this transition is regulated by the VP35 and other viral components...
May 31, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28518032/isolated-case-of-marburg-virus-disease-kampala-uganda-2014
#10
Luke Nyakarahuka, Joseph Ojwang, Alex Tumusiime, Stephen Balinandi, Shannon Whitmer, Simon Kyazze, Sam Kasozi, Milton Wetaka, Issa Makumbi, Melissa Dahlke, Jeff Borchert, Julius Lutwama, Ute Ströher, Pierre E Rollin, Stuart T Nichol, Trevor R Shoemaker
In September 2014, a single fatal case of Marburg virus was identified in a healthcare worker in Kampala, Uganda. The source of infection was not identified, and no secondary cases were identified. We describe the rapid identification, laboratory diagnosis, and case investigation of the third Marburg virus outbreak in Uganda.
June 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28481728/a-bioluminescent-imaging-mouse-model-for-marburg-virus-based-on-a-pseudovirus-system
#11
Li Zhang, Qianqian Li, Qiang Liu, Weijin Huang, Jianhui Nie, Youchun Wang
Marburg virus (MARV) can cause lethal hemorrhagic fever in humans. Handling of MARV is restricted to high-containment biosafety level 4 (BSL-4) facilities, which greatly impedes research into this virus. In this study, a high titer of MARV pseudovirus was generated through optimization of the HIV backbone vectors, the ratio of backbone vector to MARV glycoprotein expression vector, and the transfection reagents. An in vitro neutralization assay and an in vivo bioluminescent imaging mouse model for MARV were developed based on the pseudovirus...
May 8, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28447193/ebola-and-marburg-virus-vaccines
#12
REVIEW
Pierce Reynolds, Andrea Marzi
The filoviruses, Ebola virus (EBOV), and Marburg virus (MARV), are among the most pathogenic viruses known to man and the causative agents of viral hemorrhagic fever outbreaks in Africa with case fatality rates of up to 90%. Nearly 30,000 infections were observed in the latest EBOV epidemic in West Africa; previous outbreaks were much smaller, typically only affecting less than a few hundred people. Compared to other diseases such as AIDS or Malaria with millions of cases annually, filovirus hemorrhagic fever (FHF) is one of the neglected infectious diseases...
April 26, 2017: Virus Genes
https://www.readbyqxmd.com/read/28442605/the-toll-like-receptor-4-antagonist-eritoran-protects-mice-from-lethal-filovirus-challenge
#13
Patrick Younan, Palaniappan Ramanathan, Jessica Graber, Fabian Gusovsky, Alexander Bukreyev
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over in February of 2016, has demonstrated the need for the rapid development of therapeutic intervention strategies. Indirect evidence has suggested that the EBOV infection shares several commonalities associated with the onset of bacterial sepsis, including the development of a "cytokine storm." Eritoran, a Toll-like receptor 4 (TLR4) antagonist, was previously shown to result in protection of mice against lethal influenza virus infection...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#14
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28402024/marburg-virus-like-particles-produced-in-insect-cells-induce-neutralizing-antibodies-in-rhesus-macaques
#15
Weiwei Gai, Xuexing Zheng, Chong Wang, Yongkun Zhao, Qi Wang, Hualei Wang, Gary Wong, Ying Xie, Haijun Wang, Zengguo Cao, Na Feng, Hang Chi, Tiecheng Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV)...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28396467/offering-patients-more-how-the-west-africa-ebola-outbreak-can-shape-innovation-in-therapeutic-research-for-emerging-and-epidemic-infections
#16
REVIEW
Amanda M Rojek, Peter W Horby
Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections...
May 26, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28381540/therapeutic-treatment-of-marburg-and-ravn-virus-infection-in-nonhuman-primates-with-a-human-monoclonal-antibody
#17
Chad E Mire, Joan B Geisbert, Viktoriya Borisevich, Karla A Fenton, Krystle N Agans, Andrew I Flyak, Daniel J Deer, Herta Steinkellner, Ognian Bohorov, Natasha Bohorova, Charles Goodman, Andrew Hiatt, Do H Kim, Michael H Pauly, Jesus Velasco, Kevin J Whaley, James E Crowe, Larry Zeitlin, Thomas W Geisbert
As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28356221/rapid-detection-of-all-known-ebolavirus-species-by-reverse-transcription-loop-mediated-isothermal-amplification-rt-lamp
#18
Olamide K Oloniniyi, Yohei Kurosaki, Hiroko Miyamoto, Ayato Takada, Jiro Yasuda
Ebola virus disease (EVD), a highly virulent infectious disease caused by ebolaviruses, has a fatality rate of 25-90%. Without a licensed chemotherapeutic agent or vaccine for the treatment and prevention of EVD, control of outbreaks requires accurate and rapid diagnosis of cases. In this study, five sets of six oligonucleotide primers targeting the nucleoprotein gene were designed for specific identification of each of the five ebolavirus species using reverse transcription-loop mediated isothermal amplification (RT-LAMP) assay...
March 27, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28287337/generation-and-characterization-of-protective-antibodies-to-marburg-virus
#19
Jeffrey W Froude, Thibaut Pelat, Sebastian Miethe, Samantha E Zak, Anna Z Wec, Kartik Chandran, Jennifer Mary Brannan, Russell R Bakken, Michael Hust, Philippe Thullier, John M Dye
Marburg virus (MARV) and Ebola virus (EBOV) have been a source of epidemics and outbreaks for several decades. We present here the generation and characterization of the first protective antibodies specific for wild-type MARV. Non-human primates (NHP), cynomolgus macaques, were immunized with viral-replicon particles expressing the glycoproteins (GP) of MARV (Ci67 isolate). An antibody fragment (single-chain variable fragment, scFv) phage display library was built after four immunogen injections, and screened against the GP1-649 of MARV...
May 2017: MAbs
https://www.readbyqxmd.com/read/28197304/ester-prodrugs-of-ihvr-19029-with-enhanced-oral-exposure-and-prevention-of-gastrointestinal-glucosidase-interaction
#20
Julia Ma, Shuo Wu, Xuexiang Zhang, Fang Guo, Katherine Yang, Jia Guo, Qing Su, Huagang Lu, Patrick Lam, Yuhuan Li, Zhengyin Yan, William Kinney, Ju-Tao Guo, Timothy M Block, Jinhong Chang, Yanming Du
IHVR-19029 (6) is a lead endoplasmic reticulum α-glucosidases I and II inhibitor, which efficiently protected mice from lethal Ebola and Marburg virus infections via injection route, but suffered from low bioavailability and off-target interactions with gut glucosidases when administered orally. In an effort to improve efficacious exposure levels and avoid side effects, we designed and synthesized ester prodrugs. Not only were the prodrugs stable in simulated gastric and intestinal fluids and were inactive against glucosidases but they also exhibited antiviral activities against dengue virus infection in a cell based assay...
February 9, 2017: ACS Medicinal Chemistry Letters
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