Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda

Towner, Jonathan S.; Sealy, Tara K.; Khristova, Marina L.; Albariño, César G.; Conlan, Sean; Reeder, Serena A.; Quan, Phenix‐Lan; Lipkin, W. Ian; Downing, Robert; Tappero, Jordan W.; Okware, Samuel; Lutwama, Julius J.; Bakamutumaho, Barnabas; Kayiwa, John; Comer, James A.; Rollin, Pierre E.; Ksiazek, Thomas G.; Nichol, Stuart T.

doi:10.1371/journal.ppat.1000212

Cited by 470 publications

(403 citation statements)

References 21 publications

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“…This virus consists of five species: Zaire ebolavirus (ZEBOV), Sudan ebolavirus (SEBOV), Cote d'Ivoire ebolavirus (CEBOV), Bundibugyo ebolavirus (BEBOV), and Reston ebolavirus (REBOV) [5]. Among the five species, the ZEBOV, SEBOV, and BEBOV are responsible for the most Ebola outbreaks in recent years, with ZEBOV is the most pathogenic EBOV with the highest fatality rates at 90 % [19,20]. EBOVs is a nonsegmented, single-stranded RNA virus which encodes seven proteins: nucleoproteins (NP), glycoprotein (GP), polymerase (L), VP24, VP30, VP35, and VP40 [21].…”

Section: Introductionmentioning

confidence: 99%

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Tambunan¹,

Nasution²

2017

AIP Conference Proceedings

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Sensitivity differences between microporous NaY and hierarchical ZSM-5 modified electrodes as ammonia gas sensor AIP Conference Proceedings 1862, 030081 (2017) Abstract. Ebola remains as one of the deadliest diseases in the world, with almost 29,000 cases were reported and kill 11,000 of them, and yet neither treatment nor vaccine that can combat this disease effectively. This disease is caused by ebolavirus (EBOV), a primary member of Filoviridae family. The life cycle of this virus has been operated by several key proteins, one of them is VP24 protein, which has been known for its crucial role in the transcription and replication of EBOV. Therefore, targeting VP24 protein can be a solution for treating this pathogenic disease. In this study, virtual screening of Indonesian natural products as EBOV VP24 inhibitor was performed. About 2,020 ligands from many sources, including HerbalDB database, were obtained and screened by using DataWarrior software to measure its molecular and pharmacological properties, resulting 301 ligands in the process. Then, the molecular docking simulation was performed to check the ligand's binding interaction and affinity with EBOV VP24 protein; this simulation was done by using MOE 2014.09 software. This study resulted that cycloartocarpin was the best ligand to inhibit the EBOV VP24 protein. Therefore, this ligand should be checked its stability through molecular dynamics simulation and performed in vitro test to verify its bioactivity against the EBOV VP24 protein.

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Section: Introductionmentioning

confidence: 99%

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Tambunan¹,

Nasution²

2017

AIP Conference Proceedings

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“…The species vary in their pathogenicity, with ZEBOV being most pathogenic (up to 90% case fatality), followed by SEBOV and BEBOV, with up to 50%. CIEBOV and REBOV have been shown to be lethal in nonhuman primates (NHPs), but only CIEBOV has been associated with one severe human case so far (1,2). Currently, Old World macaques, notably cynomolgus and rhesus macaques, are the gold standard animal model for studying ZEBOV pathogenesis and testing vaccines and therapeutics.…”

mentioning

confidence: 99%

Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates

Marzi¹,

Engelmann

Feldmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

236

245

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Ebola viruses cause hemorrhagic disease in humans and nonhuman primates with high fatality rates. These viruses pose a significant health concern worldwide due to the lack of approved therapeutics and vaccines as well as their potential misuse as bioterrorism agents.Although not licensed for human use, recombinant vesicular stomatitis virus (rVSV) expressing the filovirus glycoprotein (GP) has been shown to protect macaques from Ebola virus and Marburg virus infections, both prophylactically and postexposure in a homologous challenge setting. However, the immune mechanisms of protection conferred by this vaccine platform remain poorly understood. In this study, we set out to investigate the role of humoral versus cellular immunity in rVSV vaccine-mediated protection against lethal Zaire ebolavirus (ZEBOV) challenge. Groups of cynomolgus macaques were depleted of CD4+ T, CD8+ T, or CD20+ B cells before and during vaccination with rVSV/ZEBOV-GP. Unfortunately, CD20-depleted animals generated a robust IgG response. Therefore, an additional group of vaccinated animals were depleted of CD4+ T cells during challenge. All animals were subsequently challenged with a lethal dose of ZEBOV. Animals depleted of CD8+ T cells survived, suggesting a minimal role for CD8+ T cells in vaccine-mediated protection. Depletion of CD4+ T cells during vaccination caused a complete loss of glycoprotein-specific antibodies and abrogated vaccine protection. In contrast, depletion of CD4+ T cells during challenge resulted in survival of the animals, indicating a minimal role for CD4+ T-cell immunity in rVSV-mediated protection. Our results suggest that antibodies play a critical role in rVSV-mediated protection against ZEBOV.

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“…The case fatality associated with Sudan virus infections ranges from 53 to 66% (5,6), and that of Bundibugyo virus is estimated near 40% based on epidemiologic findings from the 2007 Uganda outbreak (7)(8)(9). Reston virus, while highly pathogenic for nonhuman primates, does not appear to cause disease in humans (10,11).…”

mentioning

confidence: 99%

Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences

Carroll

Towner

Sealy

et al. 2013

J Virol

Self Cite

145

129

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Viruses in the Ebolavirus and Marburgvirus genera (family Filoviridae) have been associated with large outbreaks of hemorrhagic fever in human and nonhuman primates. The first documented cases occurred in primates over 45 years ago, but the amount of virus genetic diversity detected within bat populations, which have recently been identified as potential reservoir hosts, suggests that the filoviruses are much older. Here, detailed Bayesian coalescent phylogenetic analyses are performed on 97 whole-genome sequences, 55 of which are newly reported, to comprehensively examine molecular evolutionary rates and estimate dates of common ancestry for viruses within the family Filoviridae. Molecular evolutionary rates for viruses belonging to different species range from 0.46 ؋ 10 ؊4 nucleotide substitutions/site/year for Sudan ebolavirus to 8.21 ؋ 10 ؊4 nucleotide substitutions/site/year for Reston ebolavirus. Most recent common ancestry can be traced back only within the last 50 years for Reston ebolavirus and Zaire ebolavirus species and suggests that viruses within these species may have undergone recent genetic bottlenecks. Viruses within Marburg marburgvirus and Sudan ebolavirus species can be traced back further and share most recent common ancestors approximately 700 and 850 years before the present, respectively. Examination of the whole family suggests that members of the Filoviridae, including the recently described Lloviu virus, shared a most recent common ancestor approximately 10,000 years ago. These data will be valuable for understanding the evolution of filoviruses in the context of natural history as new reservoir hosts are identified and, further, for determining mechanisms of emergence, pathogenicity, and the ongoing threat to public health.

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Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda

Cited by 470 publications

References 21 publications

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Identification of novel Ebola virus (EBOV) VP24 inhibitor from Indonesian natural products through in silico drug design approach

Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates

Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences

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