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https://www.readbyqxmd.com/read/29462200/a-prophylactic-multivalent-vaccine-against-different-filovirus-species-is-immunogenic-and-provides-protection-from-lethal-infections-with-ebolavirus-and-marburgvirus-species-in-non-human-primates
#1
Benoit Callendret, Jort Vellinga, Kerstin Wunderlich, Ariane Rodriguez, Robin Steigerwald, Ulrike Dirmeier, Cedric Cheminay, Ariane Volkmann, Trevor Brasel, Ricardo Carrion, Luis D Giavedoni, Jean L Patterson, Chad E Mire, Thomas W Geisbert, Jay W Hooper, Mo Weijtens, Jutta Hartkoorn-Pasma, Jerome Custers, Maria Grazia Pau, Hanneke Schuitemaker, Roland Zahn
The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV)...
2018: PloS One
https://www.readbyqxmd.com/read/29457711/small-animal-models-for-evaluating-filovirus-countermeasures
#2
Logan Banadyga, Gary Wong, Xiangguo Qiu
The development of novel therapeutics and vaccines to treat or prevent disease caused by filoviruses, such as Ebola and Marburg viruses, depends on the availability of animal models that faithfully recapitulate clinical hallmarks of disease as it is observed in humans. In particular, small animal models (like mice and guinea pigs) are historically and frequently used for the primary evaluation of antiviral countermeasures, prior to testing in nonhuman primates, which represent the gold-standard filovirus animal model...
February 19, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29454637/tools-to-study-pathogen-host-interactions-in-bats
#3
REVIEW
Arinjay Banerjee, Vikram Misra, Tony Schountz, Michelle L Baker
Bats are natural reservoirs for a variety of emerging viruses that cause significant disease in humans and domestic animals yet rarely cause clinical disease in bats. The co-evolutionary history of bats with viruses has been hypothesized to have shaped the bat-virus relationship, allowing both to exist in equilibrium. Progress in understanding bat-virus interactions and the isolation of bat-borne viruses has been accelerated in recent years by the development of susceptible bat cell lines. Viral sequences similar to severe acute respiratory syndrome coronavirus (SARS-CoV) have been detected in bats, and filoviruses such as Marburg virus have been isolated from bats, providing definitive evidence for the role of bats as the natural host reservoir...
February 15, 2018: Virus Research
https://www.readbyqxmd.com/read/29452047/lessons-learned-from-ebola-vaccine-r-d-during-a-public-health-emergency
#4
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/29451827/sending-the-right-message-wild-game-and-the-west-africa-ebola-outbreak
#5
Kristin Post
The unprecedented scale of the Ebola epidemic in West Africa in 2014-15 caught the world by surprise. Zaire Ebolavirus had not previously been documented in Guinea, Sierra Leone, or Liberia. However, since this strain of filovirus was first identified in 1976, scientists have been studying the disease and its origins. They have identified forest-dwelling animals that carry the virus, and some that die from it, but have yet to isolate how it is transmitted from animals to humans. During the height of the Ebola outbreak in West Africa, some public health messages addressed the link among Ebola, wild animals, and humans...
January 2018: Health Security
https://www.readbyqxmd.com/read/29451777/filomicelles-deliver-a-chemo-differentiation-combination-of-paclitaxel-and-retinoic-acid-that-durably-represses-carcinomas-in-liver-to-prolong-survival
#6
Praful Nair, Cory Alvey, Xiaoling Jin, Jerome Irianto, Irena Ivanovska, Dennis E Discher
Drug resistance and relapse is common in cancer treatments with chemotherapeutics, and while drug combinations with naturally occurring, differentiation-inducing retinoic acid (RA) are highly successful against one type of liquid tumor, solid tumors present major problems for delivery. Here, inspired by filoviruses that can be microns in length, flexible filomicelles that self-assemble from an amphiphilic block copolymer (PEG-PCL) are shown to effectively deliver RA and paclitaxel (TAX) to several solid tumor models, particularly in liver...
February 16, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29375139/post-exposure-treatments-for-ebola-and-marburg-virus-infections
#7
REVIEW
Robert W Cross, Chad E Mire, Heinz Feldmann, Thomas W Geisbert
The filoviruses - Ebola virus and Marburg virus - cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus...
January 29, 2018: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29369776/successful-treatment-of-marburg-virus-with-orally-administrated-t-705-favipiravir-in-a-mouse-model
#8
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/29360169/adrenomedullin-surges-are-linked-to-acute-episodes-of-the-systemic-capillary-leak-syndrome-clarkson-disease
#9
Zhihui Xie, Wei-Sheng Chen, Yuzhi Yin, Eunice C Chan, Kaoru Terai, Lauren M Long, Timothy G Myers, Arkadiusz Z Dudek, Kirk M Druey
BACKGROUND: Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses...
January 23, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29350545/sensitive-multiplex-real-time-rt-qpcr-assay-for-the-detection-of-filoviruses
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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