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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/29280483/3-4-diaminopyridine-base-effectively-treats-the-weakness-of-lambert-eaton-myasthenia
#5
Donald B Sanders, Vern C Juel, Yadollah Harati, A Gordon Smith, Amanda C Peltier, Tessa Marburger, Jau-Shin Lou, Robert M Pascuzzi, David P Richman, Tai Xie, Valentin Demmel, Laura R Jacobus, Kathy L Aleš, David P Jacobus
INTRODUCTION: 3,4-diaminopyridine has been used to treat Lambert Eaton myasthenia (LEM) for thirty years despite the lack of conclusive evidence of efficacy. METHODS: We conducted a randomized double-blind placebo-controlled withdrawal study in LEM patients who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in Triple Timed Up-and-Go (3TUG) times during tapered drug withdrawal...
December 27, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29232390/clinicopathological-hallmarks-and-biomarkers-of-colorectal-neuroendocrine-neoplasms
#6
Alexander Koenig, Sebastian Krug, Daniela Mueller, Peter J Barth, Ute Koenig, Michael Scharf, Volker Ellenrieder, Patrick Michl, Roland Moll, Kia Homayunfar, Peter Herbert Kann, Philipp Stroebel, Thomas M Gress, Anja Rinke
Chromogranin A (CgA) is a well-established marker for diagnosis and follow up of patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Recently, it has been shown that plasma levels of CgA correlate with tumor load and predict survival of patients with NEN of the small bowel. It is assumed that this is as well valid for NEN of the colon and rectum, however, this is not supported by data. To evaluate this assumption, we analyzed 62 patients with NEN of the colon and rectum listed in the Marburg GEP-NEN registry for clinicopathological characteristics, expression and plasma levels of CgA...
2017: PloS One
https://www.readbyqxmd.com/read/29227420/us-state-public-health-departments-special-pathogen-planning
#7
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
#8
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
#9
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
#10
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
#11
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/29141824/inhibition-of-neurogenesis-in-a-case-of-marburg-variant-multiple-sclerosis
#12
Celia Oreja-Guevara, Ulises Gómez-Pinedo, Julia García-López, Rafael Sánchez-Sánchez, Roberto Valverde-Moyano, Alberto Rabano-Gutierrez, Jordi A Matías-Guiu, Ines González-Suárez, Jorge Matías-Guiu
INTRODUCTION: Neural stem cells (NSC) are located essentially in the subventricular zone (SVZ), subgranular zone (SGZ), and along the central canal of the spinal cord. These cells can proliferate in vitro and differentiate into neurons, oligodendrocytes, and astroglia, thus contributing to repair in multiple sclerosis (MS). We conducted a pathological study to analyse neurogenic response in a patient with Marburg variant MS. METHODS: We present the case of a 27-year-old immunocompetent patient with Marburg variant MS, a fulminant form of the disease...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29133548/uganda-grapples-with-new-marburg-disease-outbreak
#13
Henry Wasswa
No abstract text is available yet for this article.
November 13, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29122104/the-diagnosis-of-chronic-coronary-heart-disease
#14
Christian Albus, Jörg Barkhausen, Eckart Fleck, Jörg Haasenritter, Oliver Lindner, Sigmund Silber
BACKGROUND: Chronic coronary heart disease (CHD) and acute myocardial infarction are endemic conditions. In Germany, an estimated 900 000 cardiac catheterizations were performed in the year 2014, and a percutaneous intervention was carried out in 40% of these procedures. It would be desirable to lessen the number of invasive diagnostic procedures while preserving the reliability of diagnosis. In this article, we present the updated recommendations of the German National Care Guideline for Chronic CHD with regard to diagnostic evaluation...
October 20, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/29106386/sirna-rescues-nonhuman-primates-from-advanced-marburg-and-ravn-virus-disease
#15
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/29096001/hybrids-and-horizontal-transfer-introgression-allows-adaptive-allele-discovery
#16
Roswitha Schmickl, Sarah Marburger, Sian Bray, Levi Yant
Evolution has devised countless remarkable solutions to diverse challenges. Understanding the mechanistic basis of these solutions provides insights into how biological systems can be subtly tweaked without maladaptive consequences. The knowledge gained from illuminating these mechanisms is equally important to our understanding of fundamental evolutionary mechanisms as it is to our hopes of developing truly rational plant breeding and synthetic biology. In particular, modern population genomic approaches are proving very powerful in the detection of candidate alleles for mediating consequential adaptations that can be tested functionally...
October 31, 2017: Journal of Experimental Botany
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
#17
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/29055482/a-case-of-acute-fulminant-multiple-sclerosis-treated-with-alemtuzumab
#18
F Gobbin, A Marangi, R Orlandi, S Richelli, M Turatti, M Calabrese, A Forgione, F Alessandrini, M D Benedetti, S Monaco, A Gajofatto
We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture...
October 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29038656/unveiling-a-drift-resistant-cryptotope-within-marburgvirus-nucleoprotein-recognized-by-llama-single-domain-antibodies
#19
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
#20
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
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