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Marburg virus

Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu
The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model...
January 18, 2018: Zoological Research
Elisabeth K Nyakatura, Samantha E Zak, Anna Z Wec, Daniel Hofmann, Sergey Shulenin, Russell R Bakken, M Javad Aman, Kartik Chandran, John M Dye, Jonathan R Lai
Filoviruses (family Filoviridae ) include five ebolaviruses and Marburg virus. These pathogens cause a rapidly progressing and severe viral disease with high mortality rates (generally 30%-90%). Outbreaks of filovirus disease are sporadic and, until recently, were limited to less than 500 cases. However, the 2013-2016 epidemic in western Africa, caused by Ebola virus (EBOV), illustrated the potential of filovirus outbreaks to escalate to a much larger scale (over 28,000 suspected cases). Monoclonal antibodies (mAbs) against the envelope glycoprotein represent a promising therapeutic platform for managing filovirus infections...
March 2, 2018: Journal of Biological Chemistry
Xin Zhang, Qiang Liu, Na Zhang, Qian-Qian Li, Zhan-Dong Liu, Ying-Hong Li, Li-Mei Gao, You-Chun Wang, Hong-Bin Deng, Dan-Qing Song
Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency. Compound 2e exhibited the most potent anti-EBOV and anti-MARV effects both in vitro and in vivo...
February 26, 2018: European Journal of Medicinal Chemistry
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
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
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 corona virus (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...
March 15, 2018: Virus Research
Nadia Storm, Petrus Jansen Van Vuren, Wanda Markotter, Janusz T Paweska
Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV...
February 10, 2018: Viruses
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
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
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
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
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
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
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
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...
January 2018: Antiviral Research
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...
December 5, 2017: Structure
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
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
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
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
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