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https://www.readbyqxmd.com/read/29350545/sensitive-multiplex-real-time-rt-qpcr-assay-for-the-detection-of-filoviruses
#1
Vladimir G Dedkov, N'Faly Magassouba, Marina V Safonova, Sergey A Bodnev, Oleg V Pyankov, Jacob Camara, Bakary Sylla, Alexander P Agafonov, Victor V Maleev, German A Shipulin
Filoviruses are important etiological agents of emergent diseases with high mortality rates. Traditionally, filovirus fever diseases have primarily been a burden of African countries; however, global interconnectedness has increased the probability of the worldwide spread of filoviruses. Therefore, national healthcare organizations need tools for managing filovirus risk, including diagnostic kits based on real-time reverse transcription PCR (RT-qPCR), as this is the most suitable method for diagnosing filovirus fever diseases...
January 19, 2018: Health Security
https://www.readbyqxmd.com/read/29305306/filovirus-proteins-for-antiviral-drug-discovery-structure-function-of-proteins-involved-in-assembly-and-budding
#2
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
#3
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
#4
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/29279280/the-path-towards-effective-antivirals-against-rabies
#5
Dirk Jochmans, Johan Neyts
Rabies virus remains an important burden of disease claiming an estimated 60,000 lives each year, mainly children, and having a huge economical and societal cost. Post-exposure prophylaxis (PEP) is highly effective, however in patients that present with neurological symptoms the case-fatality ratio is extremely high (>99%). During the last decades several attempts to identify potent and effective antivirals were made. Only a few of these demonstrated improvement in clinical signs in animal studies and none of the trials in humans showed significant efficacy...
December 23, 2017: Vaccine
https://www.readbyqxmd.com/read/29260678/serologic-evidence-of-fruit-bat-exposure-to-filoviruses-singapore-2011-2016
#6
Eric D Laing, Ian H Mendenhall, Martin Linster, Dolyce H W Low, Yihui Chen, Lianying Yan, Spencer L Sterling, Sophie Borthwick, Erica Sena Neves, Julia S L Lim, Maggie Skiles, Benjamin P Y-H Lee, Lin-Fa Wang, Christopher C Broder, Gavin J D Smith
To determine whether fruit bats in Singapore have been exposed to filoviruses, we screened 409 serum samples from bats of 3 species by using a multiplex assay that detects antibodies against filoviruses. Positive samples reacted with glycoproteins from Bundibugyo, Ebola, and Sudan viruses, indicating filovirus circulation among bats in Southeast Asia.
January 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29210303/treatment-focused-ebola-trials-supportive-care-and-future-of-filovirus-care
#7
Maryam Keshtkar-Jahromi, Karen A O Martins, Anthony Cardile, Ronald Reisler, George W Christopher, Sina Bavari
During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients. Potential benefits and pitfalls of combination therapies for filoviruses will be discussed...
December 6, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29199040/progress-towards-a-vaccine-against-ebola-to-meet-emergency-medical-countermeasure-needs
#8
Daniel N Wolfe, Amanda G Zarrabian, Gary L Disbrow, Eric M Espeland
The Ebola virus epidemic in West Africa proved to be the largest in the history of filovirus outbreaks, causing the World Health Organization to declare a public health emergency of international concern in August of 2014. In collaboration with domestic and international partners, the Biomedical Advanced Research and Development Authority (BARDA) initiated several vaccine development projects in support of the overall response efforts. The urgency associated with the epidemic triggered the clinical evaluation of lead vaccine candidates starting in late 2014...
November 30, 2017: Vaccine
https://www.readbyqxmd.com/read/29175127/retro-2-and-its-dihydroquinazolinone-derivatives-inhibit-filovirus-infection
#9
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/29163915/field-deployable-quantitative-rapid-identification-of-active-ebola-virus-infection-in-unprocessed-blood
#10
Kavit Shah, Emma Bentley, Adam Tyler, Kevin S R Richards, Edward Wright, Linda Easterbrook, Diane Lee, Claire Cleaver, Louise Usher, Jane E Burton, James K Pitman, Christine B Bruce, David Edge, Martin Lee, Nelson Nazareth, David A Norwood, Sterghios A Moschos
The West African Ebola virus outbreak underlined the importance of delivering mass diagnostic capability outside the clinical or primary care setting in effectively containing public health emergencies caused by infectious disease. Yet, to date, there is no solution for reliably deploying at the point of need the gold standard diagnostic method, real time quantitative reverse transcription polymerase chain reaction (RT-qPCR), in a laboratory infrastructure-free manner. In this proof of principle work, we demonstrate direct performance of RT-qPCR on fresh blood using far-red fluorophores to resolve fluorogenic signal inhibition and controlled, rapid freeze/thawing to achieve viral genome extraction in a single reaction chamber assay...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29151351/immucillins-in-infectious-diseases
#11
Gary B Evans, Peter C Tyler, Vern L Schramm
The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors, or synthetic pathways with nucleoside intermediates. Here, we review three infectious agents and the use of the Immucillins to taget enzymes essential to the parasites. First, DADMe-Immucillin-G is a purine nucleoside phosphorylase (PNP) inhibitor that blocks purine salvage and shows clinical potential for treatment for the malaria parasite Plasmodium falciparum, a purine auxotroph requiring hypoxanthine for purine nucleotide synthesis...
December 5, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29144446/structure-and-assembly-of-the-ebola-virus-nucleocapsid
#12
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
#13
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/29128378/ebola-virus-disease-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#14
REVIEW
Guy A Richards, Tim Baker, Pravin Amin
Ebola virus is a filovirus that can cause fatal hemorrhagic fever (HF) and five distinct species exist that vary in terms of geographical distribution and virulence. Once the more virulent forms enter the human population, transmission occurs primarily through direct contact with infected body fluids and may result in significant outbreaks. The devastating has been the recent West African outbreak. Clinically, signs and symptoms are similar to those of the other VHFs [4]. The incubation period is 2-21days, followed by fever, headache, myalgia, diarrhoea, vomiting and dehydration; thereafter, there may be recovery or deterioration with collapse, neurological manifestations and bleeding, that can lead to a fatal outcome...
February 2018: Journal of Critical Care
https://www.readbyqxmd.com/read/29128377/viral-hemorrhagic-fever-in-the-tropics-report-from-the-task-force-on-tropical-diseases-by-the-world-federation-of-societies-of-intensive-and-critical-care-medicine
#15
REVIEW
Jorge Luis Hidalgo Marroquin, Guy A Richards, Juan Ignacio Silesky Jiménez, Tim Baker, Pravin Amin
Viral hemorrhagic fevers (VHFs) are a group of illnesses caused by four families of viruses namely Arenaviruses, Filoviruses, Bunyaviruses, and Flaviviruses. Humans are not the natural reservoir for any of these organisms and acquire the disease through vectors from animal reservoirs. In some conditions human to human transmission is possible increasing the risk to healthy individuals in the vicinity, more so to Health Care Workers (HCW). The pathogenesis of VHF, though poorly understood, varies according to the viruses involved...
November 4, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/29118454/production-and-purification-of-filovirus-glycoproteins-in-insect-and-mammalian-cell-lines
#16
Elizabeth C Clarke, Amanda L Collar, Chunyan Ye, Yíngyún Caì, Eduardo Anaya, Derek Rinaldi, Britney Martinez, Sarah Yarborough, Christine Merle, Manfred Theisen, Jiro Wada, Jens H Kuhn, Steven B Bradfute
Filoviruses are highly virulent pathogens capable of causing severe disease. The glycoproteins of filoviruses are the only virally expressed proteins on the virion surface and are required for receptor binding. As such, they are the main candidate vaccine antigen. Despite their virulence, most filoviruses are not comprehensively characterized, and relatively few commercially produced reagents are available for their study. Here, we describe two methods for production and purification of filovirus glycoproteins in insect and mammalian cell lines...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116224/comparison-of-transcriptomic-platforms-for-analysis-of-whole-blood-from-ebola-infected-cynomolgus-macaques
#17
Emily Speranza, Louis A Altamura, Kirsten Kulcsar, Sandra L Bixler, Cynthia A Rossi, Randal J Schoepp, Elyse Nagle, William Aguilar, Christina E Douglas, Korey L Delp, Timothy D Minogue, Gustavo Palacios, Arthur J Goff, John H Connor
Ebola virus disease (EVD) is a serious illness with mortality rates of 20-90% in various outbreaks. EVD is characterized by robust virus replication and strong host inflammatory response. Analyzing host immune responses has increasingly involved multimodal approaches including transcriptomics to profile gene expression. We studied cynomolgus macaques exposed to Ebola virus Makona via different routes with the intent of comparing RNA-Seq to a NanoString nCounter codeset targeting 769 non-human primate (NHP) genes...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109373/development-of-a-lethal-intranasal-exposure-model-of-ebola-virus-in-the-cynomolgus-macaque
#18
Kendra J Alfson, Laura E Avena, Gabriella Worwa, Ricardo Carrion, Anthony Griffiths
Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission...
October 29, 2017: Viruses
https://www.readbyqxmd.com/read/29106386/sirna-rescues-nonhuman-primates-from-advanced-marburg-and-ravn-virus-disease
#19
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/29040311/putative-endogenous-filovirus-vp35-like-protein-potentially-functions-as-an-ifn-antagonist-but-not-a-polymerase-cofactor
#20
Tatsunari Kondoh, Rashid Manzoor, Naganori Nao, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Makoto Kuroda, Keita Matsuno, Daisuke Fujikura, Masahiro Kajihara, Reiko Yoshida, Manabu Igarashi, Ayato Takada
It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs) have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35) is found in the little brown bat (Myotis lucifugus) genome. Putative mlEFL35-derived protein (mlEFL35p) contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN) production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication...
2017: PloS One
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