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rural populations exposed to ebola virus disease respond positively to localised case handling: evidence from sierra leone.at the height of the ebola epidemic in sierra leone in november 2014, a new decentralized approach to ending infection chains was adopted. this approach was based on building local, small-scale community care centres (ccc) intended to serve as triage units for safe handling of patients waiting for test results, with subsequent transfer to ebola treatment centers (etc) for those who tested positive for ebola. this paper deals with local response to the ccc, and explains, through qualitative analy ...202031961858
utility of primary cells to examine npc1 receptor expression in mops condylurus, a potential ebola virus reservoir.the significance of the integral membrane protein niemann-pick c1 (npc1) in the ebolavirus entry process has been determined using various cell lines derived from humans, non-human primates and fruit bats. fruit bats have long been purported as the potential reservoir host for ebolaviruses, however several studies provide evidence that mops condylurus, an insectivorous microbat, is also an ebolavirus reservoir. npc1 receptor expression in the context of ebolavirus replication in microbat cells r ...202031961874
modeling challenges of ebola virus-host dynamics during infection and treatment.mathematical modeling of ebola virus (ebov)-host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of ebov infection of cells and tissues throughout the body. current in-host mathematical models simplify ebov infection by assuming a single homogeneous compartment of infection. in particular, a recent modeling study assumed the liver as the largest solid o ...202031963118
the cost of insecurity: from flare-up to control of a major ebola virus disease hotspot during the outbreak in the democratic republic of the congo, 2019.the ongoing ebola outbreak in the eastern democratic republic of the congo is facing unprecedented levels of insecurity and violence. we evaluate the likely impact in terms of added transmissibility and cases of major security incidents in the butembo coordination hub. we also show that despite this additional burden, an adapted response strategy involving enlarged ring vaccination around clusters of cases and enhanced community engagement managed to bring this main hotspot under control.202031964460
antiviral activity of sertindole, raloxifene and ibutamoren against transcription and replication-competent ebola virus-like particles.a chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trvlp) system implementing the whole ebola virus (ebov) life cycle. dose-dependent inhibition of ebola trvlp replication was induced by 15 hit compounds, which primarily target different types of g protein-coupled receptors (gpcrs). based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives ...202031964466
nonclinical safety assessment of repeated administration and biodistribution of chad3-ebo-z ebola candidate vaccine.chad3-ebo-z is an investigational adenovirus-based vaccine for the prevention of ebola virus disease. two nonclinical studies were performed to evaluate the biodistribution, local tolerance and potential local and systemic toxic effects of this vaccine. in the biodistribution study, rats received a single intramuscular injection of either chad3-ebo-z or saline. enlargement of the draining lymph nodes, starting on day 2, was noticed in chad3-ebo-z-treated rats, indicating that an immune response ...202031965598
nurse-led implementation of etat+ is associated with reduced mortality in a children's hospital in freetown, sierra leone.in the wake of the ebola virus disease (evd) epidemic in sierra leone, secondary care facilities faced an increase in admissions with few members of medical staff available to assess and treat patients. this led to long waiting times in hospital outpatient departments. the study was undertaken in the outpatient department of ola during children's hospital (the tertiary paediatric hospital for sierra leone) in the period immediately following the evd epidemic of 2014-2015.202031967527
designing a study of correlates of risk for ebola vaccination.the recombinant vesicular stomatitis virus (rvsv) ebola vaccine was shown to be very efficacious in a novel ring vaccination trial in guinea. however, no correlates of vaccine protection have been established for ebola vaccines. several ebola vaccine candidates are available, but conducting randomized trials of additional candidates in outbreaks is difficult. establishing correlates of vaccine protection is essential. here we explore power and sample-size calculations to evaluate potential corre ...202031971229
being pregnant during the kivu ebola virus outbreak in dr congo: the rvsv-zebov vaccine and its accessibility by mothers and infants during humanitarian crises and in conflict areas.the ebola virus disease (evd) outbreak that began in kivu province of the democratic republic of the congo (drc) in july 2018 is the second largest in history. it is also the largest and most deadly of the ten ebola outbreaks to occur in drc, the country where ebola was first identified during the 1976 yambuku outbreak. the kivu region is one of the most challenging locations in which to organize humanitarian assistance. it is an active conflict zone in which numerous armed groups are conducting ...202031979026
the use of mice lacking type i or both type i and type ii interferon responses in research on hemorrhagic fever viruses. part 2: vaccine efficacy studies.for more than 20 years, researchers have used laboratory mice lacking type i or both type i and ii interferon (ifn) responses to study high-containment viruses that cause hemorrhagic fevers (hf) in humans. with the exception of rift valley fever virus, agents that cause viral hf in humans, such as ebola and lassa virus, do not cause disease in mature immunocompetent mice. in contrast, ifn-deficient mice typically develop severe or fatal disease when inoculated with these agents. the sensitivity ...202031982149
biomimetic design of peptide neutralizer of ebola virus with molecular simulation.ebola virus (ebov) belongs to the filoviridae family, which can cause severe hemorrhagic fever in humans and nonprimates. the neutralization of ebov by monoclonal antibody (mab) adi-15946 was reported recently. in the present study, the molecular interactions between the receptor gpcl of ebov and adi-15946 were studied by molecular dynamics (md) simulation and molecular mechanics-poisson-boltzmann surface area (mm-pbsa) analysis. hydrophobic interaction was identified as the main driving force f ...202031986884
ebola in the eastern democratic republic of congo: one health approach to infectious disease control.the democratic republic of congo (drc) is facing its tenth outbreak of ebola virus disease (evd), in north-kivu and ituri provinces. this is the second most deadly evd outbreak in history, after the one that occurred in west africa in 2014. the drc ministry of health (moh), supported by the world health organization (who) and a range of regional and international partners, are implementing evd response plans in these affected areas such as screening of suspect cases at points of entry, case dete ...202031993475
the sweet detection of rolling circle amplification: glucose-based electrochemical genosensor for the detection of viral nucleic acid.herein, an isothermal padlock probe-based assay for the simple and portable detection of pathogens coupled with a glucose oxidase (gox)-based electrochemical readout is reported. infectious diseases remain a constant threat on a global scale, as in recurring pandemics. rapid and portable diagnostics hold the promise to tackle the spreading of diseases and decentralising healthcare to point-of-care needs. ebola, a hypervariable rna virus causing fatalities of up to 90% for recent outbreaks in afr ...202031999596
optimized pre-clinical grade production of two novel lentiviral vector pseudotypes for lung gene delivery.lung gene therapy requires efficient transduction of slow-replicating epithelia and stable expression of delivered transgenes in the respiratory tract. lentiviral (lv) vectors have the ideal coding, expression, and transducing capacity required for gene therapy. a modified envelope glycoprotein from the jaagsiekte sheep retrovirus, termed jenv, is well suited for lv-mediated lung gene therapy due to its inherent lung tropism. here, two novel jenv-pseudotyped lvs that effectively transduce lung t ...202032000531
high-throughput, high-resolution interferometric light microscopy of biological nanoparticles.label-free, visible light microscopy is an indispensable tool for studying biological nanoparticles (bnps). however, conventional imaging techniques have two major challenges: (i) weak contrast due to low-refractive-index difference with the surrounding medium and exceptionally small size and (ii) limited spatial resolution. advances in interferometric microscopy have overcome the weak contrast limitation and enabled direct detection of bnps, yet lateral resolution remains as a challenge in stud ...202032003974
leveraging partnerships to maximize global health security improvements in guinea, 2015-2019.in response to the 2014-2016 west africa ebola virus disease (evd) outbreak, a us congressional appropriation provided funds to the us centers for disease control and prevention (cdc) to support global health security capacity building in 17 partner countries, including guinea. the 2014 funding enabled cdc to provide more than 300 deployments of personnel to guinea during the ebola response, establish a country office, and fund 11 implementing partners through cooperative agreements to support g ...202032004131
lessons learned from reinforcing epidemiologic surveillance during the 2017 ebola outbreak in the likati district, democratic republic of the congo.on may 12, 2017, the democratic republic of congo (drc) publicly declared an outbreak of ebola virus disease (evd) in the likati district of the bas-uélé province, 46 days after the index case became symptomatic. the delayed evd case detection and reporting highlights the importance of establishing real-time surveillance, consistent with the global health security agenda. we describe lessons learned from implementing improved evd case detection and reporting strategies at the outbreak epicenter ...202032004132
production and characterization of monoclonal antibodies against gp protein of ebola virus.the dna fragment encoding predicted main antigenic region, aa 1-300 on gp protein of ebola virus (ebov) was cloned into the vector pgex-kg. the recombinant gst-tagged gp-300 was expressed in escherichia coli bl21 (de3) by induction with 1 mm isopropyl-1-thio-b-d-galactoside and purified by dialysis. four monoclonal antibodies (mabs) named 1c4, 2a3, 2g7, and 2h9 against gp protein were generated by fusing mouse myeloma cell line sp2/0 with spleen lymphocytes from gp-300 protein-immunized mice. th ...202032004438
spatiotemporal variability in case fatality ratios for the 2013-2016 ebola epidemic in west africa.for the 2013-2016 ebola epidemic in west africa, the largest ebola virus disease (evd) epidemic to date, we aim to analyse the patient mix in detail to characterise key sources of spatiotemporal heterogeneity in the case fatality ratios (cfr).202032004692
serum-free production of rvsv-zebov in vero cells: microcarrier bioreactor versus scale-x™ hydro fixed-bed.ebola virus disease outbreaks have repeatedly occurred on the african continent over the last decades, with more serious outbreaks in recent years. being highly transmissible and associated to high fatality rates, it constitutes a serious threat to public health. vaccination, however, may allow for efficient control of its propagation. the most promising ebola vaccine candidate to date, rvsv-zebov, relies on a recombinant vesicular stomatitis virus construct, in which the native viral glycoprote ...202032006630
corrigendum: chaperones, membrane trafficking and signal transduction proteins regulate zaire ebola virus trvlps and interact with trvlp elements.[this corrects the article doi: 10.3389/fmicb.2018.02724.].202032010079
accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence.bats host virulent zoonotic viruses without experiencing disease. a mechanistic understanding of the impact of bats' virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. we carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. best fit models recapitulate ...202032011232
syntoxprofiler: an interactive analysis of drug combination synergy, toxicity and efficacy.drug combinations are becoming a standard treatment of many complex diseases due to their capability to overcome resistance to monotherapy. in the current preclinical drug combination screening, the top combinations for further study are often selected based on synergy alone, without considering the combination efficacy and toxicity effects, even though these are critical determinants for the clinical success of a therapy. to promote the prioritization of drug combinations based on integrated an ...202032012154
delayed recognition of ebola virus disease is associated with longer and larger outbreaks.the average time required to detect an ebola virus disease (evd) outbreak following spillover of ebola virus (ebov) to a primary human case has remained essentially unchanged for over 40 years, with some of the longest delays in detection occurring in recent decades. in this review, our aim was to examine the relationship between delays in detection of evd and the duration and size of outbreaks, and we report that longer delays are associated with longer and larger evd outbreaks. historically, e ...202032013784
development of an antibody cocktail for treatment of sudan virus infection.antibody-based therapies are a promising treatment option for managing ebolavirus infections. several ebola virus (ebov)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. here, we report the development and assessment of a sudan virus (sudv)-specific antibody cocktail. we produced a panel of sudv glycoprotein (gp)-specific human chimeric monoclonal antibodies (mabs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo ...202032015126
pregnancy outcomes among women receiving rvsvδ-zebov-gp ebola vaccine during the sierra leone trial to introduce a vaccine against ebola.little information exists regarding ebola vaccine rvsvδg-zebov-gp and pregnancy. the sierra leone trial to introduce a vaccine against ebola (strive) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared w ...202032017677
an assessment of ebola-related stigma and its association with informal healthcare utilisation among ebola survivors in sierra leone: a cross-sectional study.we examined the magnitude and correlates of ebola virus disease (evd)-related stigma among evd survivors in sierra leone since their return to their communities. in addition, we determined whether evd-related stigma is a predictor of informal health care use among evd survivors.202032020858
analysis of a therapeutic antibody cocktail reveals determinants for cooperative and broad ebolavirus neutralization.structural principles underlying the composition of protective antiviral monoclonal antibody (mab) cocktails are poorly defined. here, we exploited antibody cooperativity to develop a therapeutic mab cocktail against ebola virus. we systematically analyzed the antibody repertoire in human survivors and identified a pair of potently neutralizing mabs that cooperatively bound to the ebolavirus glycoprotein (gp). high-resolution structures revealed that in a two-antibody cocktail, molecular mimicry ...202032023489
an integrative review of the limited evidence on international travel bans as an emerging infectious disease disaster control measure.in our increasingly interconnected world, the potential for emerging infectious diseases (eids) to spread globally is of paramount concern. travel bans-herein defined as the complete restriction of travel from at least one geographic region to at least one other international geographic region-are a potential policy solution to control the global spread of disease. the social, economic, and health-related consequences of travel bans, as well as the available evidence on the effectiveness of trav ...202032031668
deadly lassa-fever outbreak tests nigeria's revamped health agency. 201832034330
an update on us ebola treatment center personnel management and training.in 2014, 56 us hospitals were designated as ebola treatment centers (etcs). etcs had minimum augmented capability requirements for ebola virus disease care, including for staffing and training. we sought to identify current etc staffing challenges and frequency of staff retraining.202032035689
conformational changes in the ebola virus membrane fusion machine induced by ph, ca2+, and receptor binding.the ebola virus (ebov) envelope glycoprotein (gp) is a membrane fusion machine required for virus entry into cells. following endocytosis of ebov, the gp1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the niemann-pick c1 (npc1) receptor. npc1 binding to cleaved gp1 is required for entry. how this interaction translates to gp2 domain-mediated fusion of viral and endosomal membranes is not known. here, using a bulk fluorescenc ...202032040508
transcriptional correlates of tolerance and lethality in mice predict ebola virus disease patient outcomes.host response to infection is a major determinant of disease severity in ebola virus disease (evd), but gene expression programs associated with outcome are poorly characterized. collaborative cross (cc) mice develop strain-dependent evd phenotypes of differential severity, ranging from tolerance to lethality. we screen 10 cc lines and identify clinical, virologic, and transcriptomic features that distinguish tolerant from lethal outcomes. tolerance is associated with tightly regulated induction ...202032049004
mucin-like domain of ebola virus glycoprotein enhances selective oncolytic actions against brain tumors.given that the ebola virus (ebov) infects a wide array of organs and cells yet displays a relative lack of neurotropism, we asked whether a chimeric vesicular stomatitis virus (vsv) expressing the ebov glycoprotein (gp) might selectively target brain tumors. the mucin-like domain (mld) of the ebov gp may enhance virus immune system evasion. here, we compared chimeric vsvs in which ebov gp replaces the vsv glycoprotein, thereby reducing the neurotoxicity associated with wild-type vsv. a chimeric ...202032051271
longitudinal human antibody repertoire against complete viral proteome from ebola virus survivor reveals protective sites for vaccine design.evolution of antibody repertoire against the ebola virus (ebov) proteome was characterized in an acutely infected patient receiving supportive care alone to elucidate virus-host interactions over time. differential kinetics are observed for igm-igg-iga epitope diversity, antibody binding, and affinity maturation to ebov proteins. during acute illness, antibodies predominate to vp40 and glycoprotein (gp). at day 13 of clinical illness, a marked increase in antibody titers to most ebov proteins an ...202032053790
treatment of ebola-related critical illness.to explore contemporary clincial case management of patients with ebola virus disease.202032055888
ebola virus disease and breastfeeding. 202032057298
structural basis for a convergent immune response against ebola virus.ebola virus disease is a severe health problem in africa. vaccines that display the zaire ebolavirus glycoprotein spike complex are a prime component for the effort to combat it. the vh3-15/vλ1-40-based class of antibodies was recently discovered to be a common response in individuals who received the ebola virus vaccines. these antibodies display attractive properties, and thus likely contribute to the efficacy of the vaccines. here, we use cryo-em to elucidate how three vh3-15/vλ1-40 antibodie ...202032059794
stability of ebola virus immunoglobulin g antibodies in long-term stored samples. 202032073609
evaluating the environmental persistence and inactivation of ms2 bacteriophage and the presumed ebola virus surrogate phi6 using low concentration hydrogen peroxide vapor.ebola virus (ebov) disease outbreaks, as well as the ability of ebov to persist in the environment under certain conditions, highlight the need to develop effective decontamination techniques against the virus. we evaluated the efficacy of hydrogen peroxide vapor (hpv) to inactivate ms2 and phi6 bacteriophages, the latter a recommended surrogate for ebov. the phages were inoculated onto six material types with and without the presence of whole human blood. the inoculated materials were then expo ...202032073830
antibody teamwork against ebola virus disease.antibodies are key components to prevent and treat ebola virus disease (evd). in this issue of immunity, gilchuk et al. decipher the underlying mechanism of two antibodies that cooperatively target ebolaviruses. the study provides insight into an antibody combination that potentiates antiviral activity and is able to prevent evd in nonhuman primates.202032075725
a bivalent, spherical virus-like particle vaccine enhances breadth of immune responses against pathogenic ebola viruses in rhesus macaques.the 2013-2016 ebola outbreak in west africa led to accelerated efforts to develop vaccines against these highly virulent viruses. a live, recombinant vesicular stomatitis virus-based vaccine has been deployed in outbreak settings and appears highly effective. vaccines based on replication-deficient adenovirus vectors either alone or in combination with a multivalent modified vaccinia ankara (mva) ebola vaccine also appear promising and are progressing in clinical evaluation. however, the ability ...202032075939
ebola virus disease. 202032080194
ebola virus disease.ebola virus disease (evd) is a severe and frequently lethal disease caused by ebola virus (ebov). evd outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. evd has a high case-fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. diagnosis requires a combination of case definition and laboratory ...202032080199
immune correlates of postexposure vaccine protection against marburg virus.postexposure immunization can prevent disease and reduce transmission following pathogen exposure. the rapid immunostimulatory properties of recombinant vesicular stomatitis virus (rvsv)-based vaccines make them suitable postexposure treatments against the filoviruses ebola virus and marburg virus (marv); however, the mechanisms that drive this protection are undefined. previously, we reported 60-75% survival of rhesus macaques treated with rvsv vectors expressing marv glycoprotein (gp) 20-30 mi ...202032080323
build the ebola database in africa. 201732080482
opinion: an existing drug to assess in vivo for potential adjunctive therapy of ebola virus disease and post-ebola syndrome. 201932082173
a systematic review of mental health programs among populations affected by the ebola virus disease.the ebola virus disease (evd) is associated with major mental health consequences (e.g., depression, anxiety, ptsd). studies have shown a need for relevant and effective programs to address mental health consequences associated to evd. this systematic review aimed to describe programs implemented following evd outbreaks and to evaluate their effectiveness and relevance in order to provide evidence-based data to improve mental health services.202032087433
crystal structure of the měnglà virus vp30 c-terminal domain.the family filoviridae contains many important human viruses, including marburg virus (marv) and ebola virus (ebov). měnglà virus (mlav), a newly discovered filovirus, is considered a potential human pathogen. the vp30 c-terminal domain (ctd) of these filoviruses plays an essential role in virion assembly. in common with other filoviruses, mlav vp30 ctd mainly exists as a dimer in solution. in this work, we determined the crystal structure of recombinant mlav vp30 ctd monomer, verifying that c-t ...202032093889
the antiviral compound remdesivir potently inhibits rna-dependent rna polymerase from middle east respiratory syndrome coronavirus.antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome-coronavirus 2 (cov-2). remdesivir (rdv) is an investigational compound with a broad spectrum of antiviral activities against rna viruses, including severe acute respiratory syndrome-cov and middle east respiratory syndrome (mers-cov). rdv is a nucleotide analog inhibitor of rna-dependent r ...202032094225
update on ebola treatment center costs and sustainability, united states, 2019.we surveyed 56 ebola treatment centers (etcs) in the united states and identified costs incurred since 2014 ($1.76 million/etc) and sustainability strategies. etcs reported heavy reliance on federal funding. it is uncertain if, or for how long, etcs can maintain capabilities should federal funding expire in 2020.202032097110
favipiravir, an anti-influenza drug against life-threatening rna virus infections.favipiravir has been developed as an anti-influenza drug and licensed as an anti-influenza drug in japan. additionally, favipiravir is being stockpiled for 2 million people as a countermeasure for novel influenza strains. this drug functions as a chain terminator at the site of incorporation of the viral rna and reduces the viral load. favipiravir cures all mice in a lethal influenza infection model, while oseltamivir fails to cure the animals. thus, favipiravir contributes to curing animals wit ...202032097670
serine-arginine protein kinase 1 regulates ebola virus transcription.ebola virus (ebov) causes a severe and often fatal disease for which no approved vaccines or antivirals are currently available. ebov vp30 has been described as a viral phosphoprotein, and nonphosphorylated vp30 is essential and sufficient to support secondary transcription in an ebov-specific minigenome system; however, phosphorylatable serine residues near the n terminus of vp30 are required to support primary viral transcription as well as the reinitiation of vp30-mediated transcription at in ...202032098814
online bayesian phylodynamic inference in beast with application to epidemic reconstruction.reconstructing pathogen dynamics from genetic data as they become available during an outbreak or epidemic represents an important statistical scenario in which observations arrive sequentially in time and one is interested in performing inference in an "online" fashion. widely used bayesian phylogenetic inference packages are not set up for this purpose, generally requiring one to recompute trees and evolutionary model parameters de novo when new data arrive. to accommodate increasing data flow ...202032101295
the integrity of the yxxl motif of ebola virus vp24 is important for the transport of nucleocapsid-like structures and for the regulation of viral rna synthesis.while it is well appreciated that late domains in the viral matrix proteins are crucial to mediate efficient virus budding, little is known about roles of late domains in the viral nucleocapsid proteins. here, we characterized the functional relevance of a yxxl motif with potential late-domain function in the ebola virus nucleocapsid protein vp24. mutations in the yxxl motif had two opposing effects on the functions of vp24. on the one hand, the mutation affected the regulatory function of vp24 ...202032102881
viruses go modular.the ww domain is a modular protein structure that recognizes the proline-rich pro-pro-x-tyr (ppxy) motif contained in specific target proteins. the compact modular nature of the ww domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the hippo pathway). as a result, ww domains play key roles in a plethora of both normal and disease processes. intriguingly, rna and dna viruses have evolved strategies to hijack cellular ww d ...202032111739
novel insights into immune systems of bats.in recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. these include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as ebola virus disease, marburg haemorrhagic fever and severe acute respiratory syndrome (sars) in humans. the evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-da ...202032117225
broad spectrum antiviral agent niclosamide and its therapeutic potential.the recent outbreak of coronavirus disease 2019 (covid-19) highlights an urgent need for therapeutics. through a series of drug repurposing screening campaigns, niclosamide, an fda-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as sars-cov, mers-cov, zikv, hcv, and human adenovirus, indicating its potential as an antiviral agent. in this brief review, we summarize the broad antiviral activity of niclosamide and hi ...202032125140
a 40-month follow-up of ebola virus disease survivors in guinea (postebogui) reveals long-term detection of ebola viral ribonucleic acid in semen and breast milk.with the increasing frequency and impact of ebola virus disease (evd) outbreaks illustrated by recent epidemics, a good understanding of the extent of viral persistance or ribonucleic acid (rna) detection in body fluids from survivors is urgently needed.201932128327
the ebola virus glycoprotein and its immune responses across multiple vaccine platforms.introduction: for over 40 years, ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates across western and central africa. in december 2013, an unprecedented ebola virus (ebov) epidemic began in west africa and resulted in the largest outbreak to date. the past and current epidemics in west africa and the democratic republic of the congo has focused attention on the potential vaccine platforms developed over the past ...202032129120
characterization of ebola convalescent plasma donor immune response and psoralen treated plasma in the united states.in 2014, passive immunization by transfusion of ebola convalescent plasma (ecp) was considered for treating patients with acute ebola virus disease (evd). early ebola virus (ebov) seroconversion confers a survival advantage in natural infection, hence transfusion of ecp plasma with high levels of neutralizing ebov antibodies is a potential passive immune therapy. techniques to reduce the risk of other transfusion-transmitted infections (ttis) are warranted as recent ecp survivors are ineligible ...202032129478
accounting for population structure reveals ambiguity in the zaire ebolavirus reservoir dynamics.ebolaviruses pose a substantial threat to wildlife populations and to public health in africa. evolutionary analyses of virus genome sequences can contribute significantly to elucidate the origin of new outbreaks, which can help guide surveillance efforts. the reconstructed between-outbreak evolutionary history of zaire ebolavirus so far has been highly consistent. by removing the confounding impact of population growth bursts during local outbreaks on the free mixing assumption that underlies c ...202032130210
evolving longitudinal retinal observations in a cohort of survivors of ebola virus disease.the 2-year ophthalmic sequelae of ebola virus disease (evd) in survivors of the 2013 to 2016 epidemic is unknown and may have public health implications for future outbreaks.202032134433
intervention to stop transmission of imported pneumonic plague - uganda, 2019.plague, an acute zoonosis caused by yersinia pestis, is endemic in the west nile region of northwestern uganda and neighboring northeastern democratic republic of the congo (drc) (1-4). the illness manifests in multiple clinical forms, including bubonic and pneumonic plague. pneumonic plague is rare, rapidly fatal, and transmissible from person to person via respiratory droplets. on march 4, 2019, a patient with suspected pneumonic plague was hospitalized in west nile, uganda, 4 days after carin ...202032134908
ribavirin does not potentiate favipiravir antiviral activity against ebola virus in non-human primates.in spite of recurrent and dramatic outbreaks, there are no therapeutics approved against ebola virus disease. favipiravir, a rna polymerase inhibitor active against several rna viruses, recently demonstrated significant but not complete protection in a non-human primate model of ebola virus disease. in this study, we assessed the benefit of the combination of favipiravir and ribavirin, another broad spectrum antiviral agent, in the same model.202032135218
human antibody repertoire following ebola virus infection and vaccination.limited knowledge exists on the quality of polyclonal antibody response generated following ebola virus (ebov) infection compared with vaccination. polyclonal antibody repertoire in plasma following ebov infection in survivors was compared with chad3-mva prime-boost human vaccination. higher antibody binding and affinity to gp was observed in survivors compared with vaccinated plasma that correlated with ebov neutralization. surprisingly, a predominant igm response was generated after prime-boos ...202032145646
[breakthroughs in global critical care medicine 2019].the following trends emerged in international critical care practice in 2019: increasing analysis to phenotypes of sepsis and acute respiratory distress syndrome (ards), increasing evidences of early initiating of vasopressors and antibiotics for septic shock, also including the early furosemide stress test for critically ill patients with acute kidney injury (aki). in addition, there are many significantly important trials with positive results: high dose vitamin c for septic shock, weaning str ...202032148223
compounds with therapeutic potential against novel respiratory 2019 coronavirus.currently, the expansion of the novel human respiratory coronavirus (known as sars-cov-2 [severe acute respiratory syndrome coronavirus 2], covid-2019 [coronavirus disease 2019], or 2019-ncov [2019 novel coronavirus]) has stressed the need for therapeutic alternatives to alleviate and stop this new epidemic. the previous epidemics of infections by high-morbidity human coronaviruses, such as sars-cov in 2003 and the middle east respiratory syndrome coronavirus (mers-cov) in 2012, prompted the cha ...202032152082
association between multivitamin supplementation and mortality among patients with ebola virus disease: an international multisite cohort study.micronutrient supplementation is recommended in ebola virus disease (evd) care; however, there is limited data on its therapeutic effects.202032161708
challenges and opportunities for china entering global research and development for emerging infectious diseases: a case study from ebola experience.china has emerged as a powerful platform for global pharmaceutical research and development (r&d) amid the 2014 ebola outbreak. the research and development impact of developing countries on prevention and control of infectious disease outbreaks has long been underestimated, particularly for emerging economies like china. here, we studied its research and development progress and government support in response to ebola outbreak by timeline, input, and output at each research and development stag ...202032164743
intradermal immunization of ebov vlps in guinea pigs induces broader antibody responses against gp than intramuscular injection.ebolavirus (ebov) infection in humans causes severe hemorrhagic fevers with high mortality rates that range from 30 to 80% as shown in different outbreaks. thus the development of safe and efficacious ebov vaccines remains an important goal for biomedical research. we have shown in early studies that immunization with insect cell-produced ebov virus-like particles (vlps) is able to induce protect vaccinated mice against lethal ebov challenge. in the present study, we investigated immune response ...202032174901
ginkgolic acid inhibits fusion of enveloped viruses.ginkgolic acids (ga) are alkylphenol constituents of the leaves and fruits of ginkgo biloba. ga has shown pleiotropic effects in vitro, including: antitumor effects through inhibition of lipogenesis; decreased expression of invasion associated proteins through ampk activation; and potential rescue of amyloid-β (aβ) induced synaptic impairment. ga was also reported to have activity against escherichia coli and staphylococcus aureus. several mechanisms for this activity have been suggested includi ...202032179788
the epidemiological presentation pattern of ebola virus disease outbreaks: changes from 1976 to 2019.ebola virus disease (evd) is the international health emergency paradigm due to its epidemiological presentation pattern, impact on public health, resources necessary for its control, and need for a national and international response.202032183912
ebola virus neutralizing antibodies in dogs from sierra leone, 2017.ebola virus (ebov) is a highly pathogenic zoonotic virus for which the reservoir host has not been identified. to study the role of dogs as potential hosts, we screened 300 serum samples from dogs in sierra leone and found ebov neutralizing antibodies in 12, suggesting their susceptibility to natural infection.202032186496
costs and benefits of early response in the ebola virus disease outbreak in sierra leone.the 2014-2016 ebola virus disease (evd) outbreak in west africa was the largest evd outbreak recorded, which has triggered calls for investments that would facilitate an even earlier response. this study aims to estimate the costs and health effects of earlier interventions in sierra leone.202032190010
2019-ncov: the identify-isolate-inform (3i) tool applied to a novel emerging coronavirus.2019 novel coronavirus (2019-ncov) is an emerging infectious disease closely related to mers-cov and sars-cov that was first reported in wuhan city, hubei province, china in december 2019. as of january 2020, cases of 2019-ncov are continuing to be reported in other eastern asian countries as well as in the united states, europe, australia, and numerous other countries. an unusually high volume of domestic and international travel corresponding to the beginning of the 2020 chinese new year compl ...202032191174
uganda's experience in ebola virus disease outbreak preparedness, 2018-2019.since the declaration of the 10th ebola virus disease (evd) outbreak in drc on 1st aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent evd cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed evd outbreak in the country. we describe uganda's experience in evd preparedness.202032192540
early detection of ebola virus proteins in peripheral blood mononuclear cells from infected mice.detection of viral ribo-nucleic acid (rna) via real-time polymerase chain reaction (rt-pcr) is the gold standard for the detection of ebola virus (ebov) during acute infection. however, the earliest window for viral rna detection in blood samples is 48-72 h post-onset of symptoms. therefore, efforts to develop additional orthogonal assays using complementary immunological and serological technologies are still needed to provide simplified methodology for field diagnostics. furthermore, unlike rt ...202032194356
titration methods for rvsv-based vaccine manufacturing.the recombinant vesicular stomatitis virus (rvsv) is an emerging platform for viral vector-based vaccines. promising results have been reported in clinical trials for the rvsv-zebov vaccine for ebola virus disease prevention. in this study, we describe the titration tools elaborated to assess the titre of rvsv-zebov productions. • a streamlined median tissue culture infectious dose (tcid50) assay to determine the infectious titer of this vaccine was established. • a digital polymerase chain reac ...202032195130
will covid-19 be a litmus test for post-ebola sub-saharan africa? 202032196700
modeling favipiravir antiviral efficacy against emerging viruses: from animal studies to clinical trials.in 2014, our research network was involved in the evaluation of favipiravir, an anti-influenza polymerase inhibitor, against ebola virus. in this review, we discuss how mathematical modeling was used, first to propose a relevant dosing regimen in humans, and then to optimize its antiviral efficacy in a nonhuman primate (nhp) model. the data collected in nhps were finally used to develop a model of ebola pathogenesis integrating the interactions among the virus, the innate and adaptive immune res ...202032198838
safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored ebola vaccine in adults in africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.the 2014 zaire ebola virus disease epidemic accelerated vaccine development for the virus. we aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored zaire ebola glycoprotein vaccine (chad3-ebo-z) in adults.202032199491
safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored ebola vaccine in children in africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.during the large 2013-16 ebola virus outbreak caused by the zaire ebola virus, about 20% of cases were reported in children. this study is the first, to our knowledge, to evaluate an ebola vaccine in children younger than 6 years. we aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored zaire ebola glycoprotein vaccine (chad3-ebo-z) in a paediatric population.202032199492
forty-two years of responding to ebola virus outbreaks in sub-saharan africa: a review.ebola virus disease (evd) is one of the deadliest haemorrhagic fevers affecting humans and non-human primates. thirty-four outbreaks have been reported in africa since it was first recognised in 1976. this review analysed 42 years of evd outbreaks and identified various challenges and opportunities for its control and prevention in sub-saharan africa.202032201623
scientists exposed to coronavirus wonder: why weren't we notified? 202032203382
a model for establishment, maintenance and reactivation of the immune response after vaccination against ebola virus.the 2014-2016 ebola outbreak in west africa has triggered accelerated development of several preventive vaccines against ebola virus. under the ebovac1 consortium, three phase i studies were carried out to assess safety and immunogenicity of a two-dose heterologous vaccination regimen developed by janssen vaccines and prevention in collaboration with bavarian nordic. to describe the immune response induced by the two-dose heterologous vaccine regimen, we propose a mechanistic ode based model, wh ...202032205143
tilorone, a broad-spectrum antiviral for emerging viruses.tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. this drug is used as a broad-spectrum antiviral in several countries of the russian federation. we have recently described activity in vitro and in vivo against the ebola virus. after a broad screening of additional viruses, we now describe in vitro activity against chikungunya virus (chik) and middle eastern respiratory syndrome coronavirus (mers-c ...202032205350
understanding of zaire ebolavirus-human protein interaction for drug repurposing.the ebola virus is a human aggressive pathogen causes ebola virus disease that threatens public health, for which there is no food drug administration approved medication. drug repurposing is an alternative method to find the novel indications of known drugs to treat the disease effectively at low cost. the present work focused on understanding the host-virus interaction as well as host virus drug interaction to identify the disease pathways and host-directed drug targets. thus, existing direct ...202032206696
effectiveness of basic training session regarding the awareness of ebola virus disease among nurses of public tertiary care hospitals of lahore.to evaluate the effectiveness of basic training session regarding the awareness of ebola virus disease among nurses of public tertiary care hospitals.202032207429
an insight into nanomedicinal approaches to combat viral zoonoses.emerging viral zoonotic diseases are one of the major obstacles to secure the "one health" concept under the current scenario. current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. moreover, most of the viral zoonoses originate from the wildlife and ...202032209041
acute plasmodium infection promotes interferon-gamma-dependent resistance to ebola virus infection.during the 2013-2016 ebola virus (ebov) epidemic, a significant number of patients admitted to ebola treatment units were co-infected with plasmodium falciparum, a predominant agent of malaria. however, there is no consensus on how malaria impacts ebov infection. the effect of acute plasmodium infection on ebov challenge was investigated using mouse-adapted ebov and a biosafety level 2 (bsl-2) model virus. we demonstrate that acute plasmodium infection protects from lethal viral challenge, depen ...202032209467
usp18 expression in cd169+ macrophages is important for strong immune response after vaccination with vsv-ebov.ebola virus epidemics can be effectively limited by the vsv-ebov vaccine (ervebo) due to its rapid protection abilities; however, side effects prevent the broad use of vsv-ebov as vaccine. mechanisms explaining the efficient immune activation after single injection with the vsv-ebov vaccine remain mainly unknown. here, using the clinically available vsv-ebov vaccine (ervebo), we show that the cell-intrinsic expression of the interferon-inhibitor usp18 in cd169+ macrophages is one important facto ...202032210083
n-glycans mediate the ebola virus-gp1 shielding of ligands to immune receptors and immune evasion.the ebola virus (ebov) glycoprotein (gp) sterically shields cell-membrane ligands to immune receptors such as human leukocyte antigen class-1 (hla-i) and mhc class i polypeptide-related sequence a (mica), thus mediating immunity evasion. it was suggested that the abundant n-glycosylation of the ebov-gp is involved in this steric shielding. we aimed to characterize (i) the gp n-glycosylation sites contributing to the shielding, and (ii) the effect of mutating these sites on immune subversion by t ...202032211339
potent neutralizing monoclonal antibodies against ebola virus isolated from vaccinated donors.ebola virus (ebov) can cause severe hemorrhagic fever in humans, and no approved treatment is currently available. although several antibodies have achieved good protection in animal models, the potential emerging isolates of ebolavirus and the unknown effects of experimental antibodies in humans underscore the need to develop additional antibodies to address the threat of ebola. here, we isolated a series of memory b cell-derived monoclonal antibodies from healthy chinese adults vaccinated with ...202032213108
early transcriptional changes within liver, adrenal gland, and lymphoid tissues significantly contribute to ebola virus pathogenesis in cynomolgus macaques.ebola virus (ebov) continues to pose a significant threat to human health, as evidenced by the 2013-2016 epidemic in west africa and the ongoing outbreak in the democratic republic of the congo. ebov causes hemorrhagic fever, organ damage, and shock culminating in death, with case fatality rates as high as 90%. this high lethality combined with the paucity of licensed medical countermeasures makes ebov a critical human pathogen. although ebov infection results in significant damage to the liver ...202032213610
challenges to ebola preparedness during an ongoing outbreak: an analysis of borderland livelihoods and trust in uganda.ebola virus disease in the democratic republic of congo (drc) was declared a public health emergency of international concern on july 17, 2019. the first case to cross the border into uganda in june 2019 demonstrates the importance of better understanding border dynamics in a context of ebola. this paper adopts a political economy approach to contextualize epidemic response programs conducted in moderate- and high-risk border districts in uganda, through a qualitative study with 287 participants ...202032214381
awareness about ebola virus disease among the health care professionals in karachi, pakistan.background: ebola virus disease is an acute and life-threatening illness, which, if untreated, is fatal. it was first discovered in 1976, which aware the world with sporadic outbreaks of ebola in some parts of africa. according to centers for disease control and prevention (cdc), the natural reservoir for ebola virus remains unknown; however, it is yet to be affirmed that the natural habitat is animal-borne where bats are most likely to carry over this virus. therefore, the aim of this study was ...202032214443
ebola hemorrhagic fever: properties of the pathogen and development of vaccines and chemotherapeutic agents.ebola hemorrhagic fever (ehf) epidemic currently ongoing in west africa is not the first among numerous epidemics in the continent. yet it seems to be the worst ehf epidemic outbreak caused by ebola virus zaire since 1976 as regards its extremely large scale and rapid spread in the population. experiments to study the agent have continued for more than 20 years. the ehf virus has a relatively simple genome with seven genes and additional reading frame resulting from rna editing. while being of a ...201532214474
comparison of trends in the quantity and variety of science citation index (sci) literature on human pathogens between china and the united states.the proportion of pathogenic microorganisms in the microbial world is relatively small, while their threat to human health, economic development and social stability is severe. the quantity and variation of science citation index (sci) literature related to pathogenic microorganisms may reflect the level of relevant research and the degree of attention. here we compared trends in the quantity and variety of sci literature relating to certain important pathogenic microorganisms published by scien ...201232214557
one health, vaccines and ebola: the opportunities for shared benefits.the 2013 ebola virus outbreak in west africa, as of writing, is declining in reported human cases and mortalities. the resulting devastation caused highlights how health systems, in particular in west africa, and in terms of global pandemic planning, are ill prepared to react to zoonotic pathogens. in this paper we propose one health as a strategy to prevent zoonotic outbreaks as a shared goal: that human and great ape vaccine trials could benefit both species. only recently have two phase 2/3 e ...201532214867
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