Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 58 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 6341 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 49 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 58 EBOV 34 Ebola 10 RNA 9 virus 8 EVD 6 Fig 5 figure 5 MERS 4 cell 4 SARS 4 NPC1 4 MARV 4 IFN 3 vaccine 3 infection 3 VSV 3 VP35 2 VP40 2 VLP 2 Marburg 2 MHC 2 HIV-1 2 ELISA 1 tetherin 1 study 1 sample 1 response 1 respiratory 1 remdesivir 1 pfu 1 patient 1 outbreak 1 march8 1 fever 1 epitope 1 entry 1 ebola 1 dna 1 disease 1 bat 1 ape 1 antisera 1 african 1 a30u 1 Vpu 1 Virus 1 Vero 1 VSVΔG 1 United 1 TNC Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 4284 virus 2742 cell 1716 infection 1226 protein 941 antibody 879 disease 834 % 801 study 797 vaccine 727 outbreak 710 entry 694 patient 634 response 593 filovirus 549 model 542 fusion 537 glycoprotein 524 assay 523 host 497 analysis 478 day 475 treatment 461 datum 453 activity 449 sequence 439 type 438 case 431 animal 428 mouse 427 receptor 426 fever 407 level 406 time 399 replication 396 bat 394 c 392 expression 370 factor 361 membrane 361 gp 360 figure 359 genome 357 sample 353 particle 336 drug 330 system 330 result 330 domain 329 structure 323 surface Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 2949 EBOV 2083 Ebola 1128 GP 1033 al 807 et 768 . 580 RNA 502 VSV 500 Fig 452 EVD 447 MARV 439 Marburg 295 VP35 275 NPC1 263 IFN 256 HIV-1 237 NP 229 Africa 222 C 221 MERS 195 VP40 191 ebola 185 CoV 183 SARS 182 Zaire 170 G 160 T 150 Virus 144 remdesivir 139 ELISA 135 PCR 134 Vero 131 VP24 130 endosomal 125 VLP 120 Congo 119 pH 116 tetherin 113 Table 112 Ebolavirus 108 West 108 PBS 108 GP2 105 Sierra 105 Leone 103 E6 97 mg 96 Niemann 95 Republic 94 RT Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 806 we 593 it 265 i 206 they 47 them 19 he 18 us 15 you 13 itself 5 themselves 4 one 3 evlps 2 sgp 1 trim30 1 tmrcas 1 pdcs 1 ours 1 myosin-10 1 mrnas 1 me 1 imagej 1 igg1 1 i450 1 his 1 him Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 11059 be 1859 have 1345 use 664 show 501 base 472 bind 438 infect 435 include 361 mediate 333 express 332 do 331 induce 320 inhibit 317 suggest 305 contain 303 provide 298 observe 293 identify 292 indicate 286 require 277 increase 275 associate 274 report 267 follow 266 demonstrate 263 find 252 describe 235 detect 234 test 234 result 233 compare 229 determine 218 cause 214 reduce 212 neutralize 205 occur 204 perform 203 treat 199 emerge 191 target 182 generate 176 confirm 170 know 169 produce 166 obtain 165 protect 163 give 159 develop 158 block 157 collect Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1214 viral 977 not 950 - 828 human 633 high 581 also 544 other 400 clinical 384 different 371 such 364 however 355 more 342 specific 331 immune 331 anti 316 well 313 low 305 antiviral 289 only 269 hemorrhagic 261 single 255 most 253 first 252 cellular 235 similar 235 like 229 small 228 respiratory 227 dependent 225 further 219 previously 219 as 218 non 218 early 217 available 206 recombinant 205 several 205 infectious 204 potential 203 then 202 severe 201 important 200 molecular 195 multiple 191 thus 188 negative 185 long 185 lethal 178 therefore 174 positive Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 67 most 64 high 55 least 28 good 25 large 21 Most 12 low 12 bad 6 great 5 early 4 small 4 simple 3 strong 3 long 2 steep 2 old 2 deadly 2 -β 1 young 1 wide 1 vMVA 1 taı̈for 1 short 1 near 1 molossid 1 mean+SD 1 few 1 close 1 broad 1 big 1 W114A 1 Least 1 -w 1 -D-2=-deoxy-2=-fluoro-2=-C Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 188 most 39 least 7 well 1 scfv 1 lowest Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 7 www.who.int 6 www.cdc.gov 6 doi.org 3 www.ncbi.nlm.nih.gov 2 www.msdiscovery.com 2 www.collaborativedrug.com 2 figshare.com 2 dx.doi.org 2 creativecommons 1 www.who 1 www.nature.com 1 www.mbe 1 www.hyphy.org 1 www.fda.gov 1 www.dovepress.com 1 www.dhs.gov 1 www.cidrap.umn.edu 1 www 1 who.int 1 rnacomposer.cs.put.poznan.pl 1 pubchem.ncbi.nlm.nih.gov 1 jid.oxfordjournals.org 1 doi 1 datamonkey.org 1 creativecommons.org 1 creat 1 apps.who.int 1 advisor.bkslab.org Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 2 http://www.msdiscovery.com/spectrum.html 2 http://creativecommons 1 http://www.who.int/news-room/detail/29-08-2019-as 1 http://www.who.int/news-room/detail/27-04-2020-who-timeline---covid- 1 http://www.who.int/en/news-room/fact-sheets/detail/ebola-virus-disease 1 http://www.who.int/emergencies/mers-cov/en/ 1 http://www.who.int/csr/resources/publications/HSE_ 1 http://www.who.int/csr/disease/ebola/ 1 http://www.who.int/csr/ 1 http://www.who 1 http://www.ncbi.nlm.nih.gov/genomes/FLU/ 1 http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ebola/ 1 http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ 1 http://www.nature.com/news/ebola-trials-to-start-in-december-1.16342 1 http://www.mbe 1 http://www.hyphy.org/wiki/codondating 1 http://www.fda.gov/ 1 http://www.dovepress.com/testimonials 1 http://www.dhs.gov/science-and 1 http://www.collaborativedrug.com/pages/public_access 1 http://www.collaborativedrug.com/ 1 http://www.cidrap.umn.edu/news-perspective/2018/08/drc-ebola-cases-surpass 1 http://www.cdc.gov/vhf/ebola/treatment/ 1 http://www.cdc.gov/vhf/ebola/clinicians/evd/infection-control.html 1 http://www.cdc.gov/vhf/ebola/clinicians/cleaning/hospitals.html 1 http://www.cdc.gov/media/releases/ 1 http://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control 1 http://www.cdc.gov/ 1 http://www 1 http://who.int/mediacentre/factsheets/fs103/en/ 1 http://rnacomposer.cs.put.poznan.pl/ 1 http://pubchem.ncbi.nlm.nih.gov/bioassay/651611 1 http://jid.oxfordjournals.org 1 http://figshare.com/articles/Ebola_active_cpds_pharmacophore/ 1 http://figshare.com/articles/A_pharmacophore_of_ebola_active_ 1 http://dx.doi.org/10.7554/eLife.11785.001 1 http://dx.doi.org/10.1016/j.bmcl.2017.04 1 http://doi.org/10.1371/journal.pone.0194880.g001 1 http://doi.org/10.1371/journal.pone.0194880 1 http://doi.org/10.1371/journal.pone.0189073.g005 1 http://doi.org/10.1371/journal.pone.0189073 1 http://doi.org/10.1038/s41598-019-56481-0.Correspondence 1 http://doi.org/10.1038/ 1 http://doi 1 http://datamonkey.org/ 1 http://creativecommons.org/licenses/by/4.0/ 1 http://creat 1 http://apps.who.int/gho/data/view.ebola-sitrep.ebola-summary-20150107?lang=en 1 http://advisor.bkslab.org Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 1 k_wada@nagahama-i-bio.ac.jp Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 11 cells were then 11 glycoprotein is necessary 8 cells are early 8 ebov infected mice 8 vaccine expressing ebola 6 glycoprotein is not 4 cells were further 4 fusion was independent 4 study did not 4 study had high 3 antibodies are necessary 3 antibodies provides protection 3 cells expressing ebov 3 cells were co 3 cells were not 3 cells were pre 3 cells were thermolysin 3 ebov is highly 3 glycoprotein mediates entry 3 outbreak was unique 3 study do not 3 study has not 3 vaccine is well 3 virus does not 3 virus was first 3 viruses including ebov 3 viruses using recombinant 3 viruses were repeatedly 3 vsv expressing marv 2 . were able 2 analysis using prism 2 analysis using several 2 antibodies demonstrated excellent 2 assay test value 2 assays were similar 2 cells are also 2 cells are not 2 cells are resistant 2 cells were additionally 2 cells were also 2 cells were approximately 2 disease had significantly 2 ebov infected human 2 ebov infected humans 2 ebov infected ifnar(-/- 2 ebov infected patients 2 ebov is able 2 ebov using rt 2 entry using entry 2 filoviruses including ebov Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 4 glycoprotein is not essential 2 glycoprotein is not critical 2 protein is not essential 1 antibodies had no effect 1 antibody had no effect 1 antibody was not significantly 1 cells are not productively 1 cells are not useful 1 cells had no appreciable 1 cells had no impact 1 cells is not ideal 1 cells showed no evidence 1 cells were not thermolysin 1 filoviruses are not commonly 1 fusion did not monotonically 1 gp is not directly 1 infection are not fully 1 infection is not uniformly 1 infection was not completely 1 models are not necessarily 1 patients are not available 1 patients were not able 1 patients were not yet 1 proteins do not permanently 1 responses is not necessarily 1 studies have not yet 1 studies were not exhaustive 1 study are not conclusive 1 study has not yet 1 viruses are not suitable A rudimentary bibliography -------------------------- id = cord-001546-ndz3oarf author = Ayithan, Natarajan title = Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date = 2015-02-26 keywords = EBOV; IFN; Ifnar; VLP summary = Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. doi = 10.1371/journal.pone.0118345 id = cord-000547-adfigzc1 author = Beniac, Daniel R. title = The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date = 2012-01-11 keywords = EBOV; Ebola; RNA; figure summary = METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). doi = 10.1371/journal.pone.0029608 id = cord-000804-0hlj6r10 author = Brauburger, Kristina title = Forty-Five Years of Marburg Virus Research date = 2012-10-01 keywords = EBOV; Ebola; MARV; Marburg; RNA; VP40; virus summary = While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections doi = 10.3390/v4101878 id = cord-296399-vvbjulm9 author = Brinkmann, Constantin title = The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date = 2017-12-07 keywords = EBOV; VSV; Vpu; tetherin summary = Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. At 1 h post infection, the inoculum was removed and the cells were transfected with expression plasmids for VSV-N, -P and -L (see above) as well as the respective, plasmid-encoded VSV Ã anti-genome (the genome is preceded by a T7 promotor sequence and followed by a hepatitis delta virus ribozyme and a T7 terminator sequence for cytoplasmic production of negative-sensed viral genomes that are template for transcription and genome replication) using Lipofectamine2000 (ThermoFisher Scientific, Dreiech) as transfection reagent. In order to analyze tetherin antagonism by VSV proteins, we employed a previously reported virus-like particle (VLP) release assay, which measures release of HIV-Gag-based VLPs from transfected 293T cells and its blockade by tetherin [27, 32] . doi = 10.1371/journal.pone.0189073 id = cord-325423-d212h4bp author = Carrion, Ricardo title = A small nonhuman primate model for filovirus-induced disease date = 2011-11-01 keywords = EBOV; MARV; pfu summary = To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. Nonhuman primates (NHPs) are the preferred animal model for human filovirus infection because infection with EBOZ and MARV isolated from humans results in fatal hemorrhagic disease. In animals inoculated with the 10 PFU and surviving to 5 dpi, hepatic disease was more severe and characterized by multifocal to coalescing hepatocellular coagulative necrosis infiltrated by small to moderate numbers of neutrophils. Consistent with the macaque model, experimental inoculation of marmosets with MARV also results in delayed onset of disease, with death occurring 3 to 4 days later than that seen with marmosets infected with EBOV. Further evidence that the marmoset mimics human disease is that microscopic examination of tissue from EBOV-infected animals reveals widespread fibrin deposition that is a hallmark of coagulation abnormalities (Geisbert et al., 2003c,d; Jaax et al., 1996) . doi = 10.1016/j.virol.2011.08.022 id = cord-002463-qhtj1pef author = Dash, Raju title = In silico-based vaccine design against Ebola virus glycoprotein date = 2017-03-21 keywords = EBOV; Ebola; HLA; MHC; epitope summary = Top scored eiptope subjected to 100 ns MD simulation **RMSF **RMSD **Hydrogen bond occupency analysis Secquence, having highest vaxijen score Prediction of B cell epitope, using-**T cell epitope prediction by proteasomal C terminal cleavage, TAP transport efficiency and MHC class 1 binding **Epitopes with IC50 value less than 50 for their binding to MHC class 1 molecule from IEDB analysis along with binding to highest number of alleles in both analyses were chosen **Epitope conservancy analysis **Population coverage analysis **Kolaskar and Tongaonkar antigenicity scale 48 **Emini surface accessibility prediction 47 **Karplus and Schulz flexibility prediction 49 **Bepipred linear epitope prediction 50 **Chou and Fasman beta turn prediction 52 Vaxijen analysis with a threshold score of >0. We also validated each epitope by molecular docking simulation and MM-GBSA/MM-PBSA studies with HLA-A*32:15 protein, as it was found common in the results from MHC-I binding interaction analysis. doi = 10.2147/aabc.s115859 id = cord-336986-rmxin1da author = De Clercq, Erik title = New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections date = 2019-08-07 keywords = EBOV; EICAR; RNA summary = Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. Abstract: Eight differentc ompounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/oro ther hemorrhagic fever virus (HFV) infections.T hey can be considered as either (i)adenine analogues (3-deazaneplanocin A, galidesivir,G S-6620 andr emdesivir) or (ii)guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). [26] It wasa lso found active against other emerging viruses such as respiratory syncytial virus (RSV) and hepatitis Cv irus (HCV),a nd the presence of the 1''-cyano group in remdesivir wasf ound to be critical in providing selectivity toward the viral (RNA) polymerases. doi = 10.1002/asia.201900841 id = cord-004069-nuep8nim author = DeWald, Lisa Evans title = In Vivo Activity of Amodiaquine against Ebola Virus Infection date = 2019-12-27 keywords = DEAQ; EBOV; EVD; Fig summary = A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . doi = 10.1038/s41598-019-56481-0 id = cord-011129-btaxvmsr author = Di Paola, Nicholas title = Viral genomics in Ebola virus research date = 2020-05-04 keywords = Congo; EBOV; EVD; Ebola; Republic; outbreak; virus summary = Here, we review how recent advances in genomic technologies have shaped past and current responses to outbreaks of Ebola virus disease (EVD), including insights into filovirus diversity and evolution. After this identification, considerations other than sequencing speed (for example, sequencing accuracy and processivity) become paramount in determining virus transmission networks and in detecting changes in the viral genome (between cases in the current outbreak and between the current and previous outbreaks) that could subvert MCMs. However, whereas unbiased sequencing approaches using high fidelity platforms can lead to the discovery of co-infections and reveal important clinical considerations during the treatment of patients near the point of need, targeted methods of pathogen characterization using the portable sequencing platforms iSeq 100 and MiSeq (which use bait-enrichment techniques) and MinION (which uses amplicon sequencing) can still provide useful genomic data albeit with a lower sequencing output (that is, a lower number of reads) than unbiased sequencing. doi = 10.1038/s41579-020-0354-7 id = cord-352492-6ihyiwgb author = Eickmann, Markus title = Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively date = 2018-05-06 keywords = EBOV; MERS; THERAFLEX summary = title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively STUDY DESIGN AND METHODS: PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity. The results of the infectivity assay demonstrated that UVC irradiation dose-dependently inactivated EBOV and MERS-CoV in plasma-reduced PCs (Table 1 ). Although EBOV is highly infectious and low doses of less than 10 plaque-forming units of the virus are sufficient to cause disease, 32 the ability of the UVC-and MB/ light-based systems to reduce MERS-CoV and EBOV infectivity in blood products by several log steps may be sufficient to eliminate or significantly reduce the risk of transmission via the transfusion of PCs or plasma. doi = 10.1111/trf.14652 id = cord-001513-p7v5p036 author = Ekins, Sean title = A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date = 2014-12-12 keywords = EBOV; FDA; VP35 summary = Common features pharmacophore for EBOV actives Two papers from 2013 described compounds active as inhibitors of different EBOV strains in vitro and in vivo, namely amodiaquine and chloroquine in one study 8 , clomiphene and toremifene in another 9 . These suggest that the receptor-ligand based approach results in a general similarity across the nine structures, likely indicating the similar binding mode and importance of features for interfering with this generally hydrophobic pocket for protein-protein interactions. In silico docking of molecules in VP35 structure Redocking the 4IBI ligand in the protein resulted in an RMSD of 3.02Å, which generally indicates the difficulty of predicting orientations for compounds binding in what is a relatively hydrophobic and shallow pocket ( Figure S1 ). Pharmacophores, receptor ligand models and docking data for FDA-approved drugs inhibiting the Ebola virus, 10.5256/f1000research.5741.d38449 35 . doi = 10.12688/f1000research.5741.2 id = cord-288029-6l91knu3 author = Elfiky, Abdo A. title = Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction date = 2020-04-14 keywords = EBOV; GP1; HSPA5 summary = title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction In this study, structural and sequence analysis and molecular docking are used to predict the possible binding site between the cell-surface HSPA5 and EBOV GP1. In this work, the binding site between cell-surface HSPA5 and viral GP1 protein is predicted based on sequence, and thus, Pep42 is an example of a class of drugs that may reduce EBOV infections. In addition, HPEPDOCK constructs different possible conformations of the peptide and tests the binding affinity of each of the predicted structures against the target protein (Zhou et al. The cyclic peptide Pep42 was reported to selectively target cell-surface HSPA5 (which appears in some types of cancer) and used as a drug carrier for the anti-cancer agent, doxorubicin (Ibrahim et al. These hydrophobic residues of EBOV GP1 (C121, L122, A124, A125, I129, F132, and C135) are suggested to be the binding site for cell-surface HSPA5. Ebola virus glycoprotein GP1-host cell-surface HSPA5 binding site prediction doi = 10.1007/s12192-020-01106-z id = cord-284845-on97zu6w author = Falcinelli, Shane D. title = Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections date = 2016-07-29 keywords = EBOV; Ebola; MERS; MPXV; infection; response summary = Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. As emerging viral infections often result in severe illness including respiratory failure [severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza] and multiorgan failure [Ebola virus disease (EVD)], understanding complex pathogenesis of these infections is required for effective vaccine and therapeutic design and for improved patient care. Specifically, detailed natural history studies merging multiple data streams including OMICS approaches (high-throughput gene expression and kinomics) and focused translational investigations utilizing relevant models that can be validated to human disease are needed to clarify disease pathogenesis, advance therapeutic discovery, and facilitate regulatory approval. doi = 10.1021/acsinfecdis.6b00104 id = cord-289413-mbrw85og author = Flego, Michela title = Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date = 2019-09-05 keywords = EBOV; ELISA; Ebola; IFN; VP35 summary = RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. This study reports the selection by phage display and characterization of 5 different human scFv antibodies binding to an active form of the Zaire EBOV VP35 [24, 25] . In a competitive assay, ELISA plates coated with VP35 or with the control antigen GO were blocked; they were then incubated with purified scFv-expressing phage both in the absence and in the presence of the competitor soluble non-phage-fused scFv at the maximum concentration of 500 μg/ml. doi = 10.1186/s12896-019-0554-2 id = cord-354068-4qlk6y7h author = Friedrich, Brian M. title = Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date = 2012-09-21 keywords = EBOV; MARV; ebola; infection; vaccine; virus summary = Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge. doi = 10.3390/v4091619 id = cord-004126-u6ts87ur author = Furuyama, Wakako title = A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades date = 2020-01-10 keywords = EBOV; Fig; H5N1; Supplementary; VSV summary = Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine. We found that a single vaccination with VSV-vectors expressing the full-length HA (HAfl) induced crossreactive H5-specific antibodies and conferred complete protection against lethal challenge with various H5 clade 2 viruses. In contrast to all the sHA-based vaccines, single doses of the VSV-EBOV-HAfl or VSV-HAfl vectors were sufficient to provide complete protection from lethal homologous H5N1 challenge in mice (Fig. 2) . However, this study did not provide any data supporting an advantage of including VSV-EBOV as part of the vector design over just expressing VSV-HAfl as both vectors performed similarly well with no statistically significant difference in efficacy following single-dose or prime/boost administration (Fig. 2 ) nor in antibody responses (Fig. 3, Table 1 ). doi = 10.1038/s41541-019-0155-z id = cord-335093-tc1qo2k0 author = Gehring, Gerrit title = The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry date = 2014-08-01 keywords = EBOV; Ebola; cell; entry; figure summary = Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. While most drugs had no major effect on filovirus GP-mediated cell entry, amiodarone was found to reduce the detectable signal by over 99%, and thus more strongly than FYdmk, which achieved 86% -98% inhibition. Filoviral GP-mediated entry into primary human umbilical vein endothelial cells and in macrophages derived from primary human monocytes was significantly inhibited at amiodarone concentrations below 1 mg/mL for both MARV and EBOV GP while amiodarone had no effect on the transduction of primary hepatocytes ( Figure S3 , available as Supplementary data at JAC Online). doi = 10.1093/jac/dku091 id = cord-344316-mwnnmwnw author = Herst, C.V. title = An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design date = 2020-04-28 keywords = EBOV; SARS summary = title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors'' CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. Wilson We set out to see if we could drive CTL expansion directed against NP43-53 to occur after vaccinating C57BL/6 mice with Ebola Zaire NP43-53 (VYQVNNLEEIC), 50 and to subsequently conduct an in-vivo EBOV challenge study to see if this peptide was protective. We show here that the H2-D b restricted epitopes VSV (RGYVYQGL) and OVA (SIINFEKL), when administered to C57BL/6 mice, each produce a CD8+ We used this adjuvanted microsphere peptide vaccine platform to immunize C57BL/6 mice with NP43-53, the CTL+ class I peptide antigen from the Ebola Ziare NP protein identified as protective by Wilson et al. doi = 10.1016/j.vaccine.2020.04.034 id = cord-001764-njzyu4mv author = Hofmann-Winkler, Heike title = Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976 date = 2015-10-01 keywords = EBOV; Ebola; cell summary = Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. However, EBOV-GP 2014 was less susceptible than EBOV-GP 1976 to blockade by a third inhibitor, CatL ( Figure 3B ), which inhibits catB and catL activity to similar extents [40] , suggesting subtle differences in the protease dependence of these GPs. HIV-derived particles rapidly lose infectivity when stored at room temperature [41] , and this loss might be due to inactivation of the viral envelope protein. Comparably Inhibited by IFITM Proteins and Neutralizing Antibody KZ52 IFITM proteins 1, 2, and 3 inhibit cellular entry of EBOV [42] and several other viral pathogens [42, 43] and might reduce EBOV amplification in the infected host, raising the question of whether viruses circulating in 2014 are less susceptible to IFITM protein inhibition than those responsible for the 1976 outbreak in Zaire. doi = 10.1093/infdis/jiv101 id = cord-342052-v4y1xc90 author = Horigan, Verity title = Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States date = 2017-10-02 keywords = EBOV; Ebola; MARV; MERS; TCID summary = The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. Since 2003 there have been a number of large-scale human outbreaks of bat-borne diseases e.g. Zaire ebolavirus (EBOV) and Severe Acute Respiratory Syndrome (SARS) in Western Africa and Asia respectively, whilst a significant number of human cases of Nipah virus (NiV) are reported in Bangladesh every year (IEDCR, 2014) . To address this need, a generic quantitative risk assessment framework for the entry of bat-borne zoonotic viruses to the EU was developed (Simons et al., 2016) , considering the pathways: human travel, live animal movement, legal trade of food products and illegal trade of bushmeat. doi = 10.1016/j.mran.2017.09.002 id = cord-334560-1j9zmuub author = Hunt, Catherine L. title = Filovirus Entry: A Novelty in the Viral Fusion World date = 2012-02-07 keywords = EBOV; NPC1; virus summary = Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] . doi = 10.3390/v4020258 id = cord-327641-hqnem2zs author = Ji, Ying-Jie title = Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone date = 2016-11-03 keywords = EBOV; EVD; Ebola; patient summary = BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. In the 2014 outbreak, the first lab-confirmed EVD patient was reported in May, 2014 in Guinea and since then the Zaire Ebola Virus (ZEBOV) has rapidly spread across Sierra Leone and to other West Africa countries. A retrospective, observational study was conducted using data collected from all patients with confirmed EVD who were admitted to the Holding and Treatment Center of Jui Government Hospital from October 1, 2014 to March 21, 2015. In our study, the multivariate analyses showed that EBOV viral load, abdominal pain, confusion, conjunctivitis, and vomiting were independently associated with the death outcome of EVD patients. doi = 10.1186/s40249-016-0195-9 id = cord-256187-ofp7tupv author = Kühl, A. title = How Ebola Virus Counters the Interferon System date = 2012-09-07 keywords = EBOV; Ebola; IFN; VP35 summary = Furthermore, VP24 can shut down the host''s IFN-a/b and IFN-c Recognition of viral pathogen-associated molecular patterns (PAMPs) by PRRs (purple) in infected cells initiates a signalling cascade including adaptor molecules (blue) and kinases (green), which activate transcription factors (red) that induce the expression of type I IFNs and ISGs (left panel). Additionally, VP35 blocks multiple steps of the innate antiviral defence (Fig. 4) , such as the signalling pathways leading to the expression of type I IFNs and type I IFN-induced genes, double-stranded (ds) RNA-dependent protein kinase (PKR) translation inhibition and RNA silencing Cárdenas et al., 2006; Feng et al., 2007; Haasnoot et al., 2007) . The tetherin protein (HM1.24, BST-2, CD317) was identified as a type I interferon-inducible host cellular factor, which restricts release of progeny HIV-1 particles from infected cells (Neil et al., 2008; Van Damme et al., 2008) . doi = 10.1111/j.1863-2378.2012.01454.x id = cord-001542-f089bs8r author = Lai, Kang Yiu title = Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date = 2014-11-28 keywords = EBOV; Ebola; GP1,2; IFN; RNA; cell; infection; virus summary = These may include monoclonal antibody (mAbs)-based therapies (e.g. ZMapp), anti-sense phosphorodiamidate morpholino oligomers (PMO AVI-6002), lipid nanoparticle small interfering RNA (LNP-siRNA: TKM-Ebola), and an EBOV glycoprotein-based vaccine using live-attenuated recombinant vesicular stomatitis virus (rVSV-EBOGP) or a chimpanzee adenovirus (rChAd-EBOGP)-based vector. The GP2 of the EBOV is able to counter the interferon (IFN)-inducible antiviral protein tetherin which restricts the VP40-dependent budding of the progeny viral particles from infected cells [16] [17] [18] . Currently available therapeutic agents that are effective in targeting the EBOV infection in cell or animal studies may include convalescent plasma, favipiravir, chloroquine, amiodarone, dronedarone, verapamil, clomiphene, toremifene, IFN-β, Na + /K + exchangers, Na + /K + -ATPase pump inhibitors, and antioxidants. The anti-EBOV activity of clomiphene and toremifene is dependent not on its estrogen receptor antagonistic action but upon the ability of both drugs to induce a Niemann-Pick C-like phenotype to inhibit viral entry at late endosome. doi = 10.1186/2049-9957-3-43 id = cord-003917-bswndfvk author = Lalle, Eleonora title = Pulmonary Involvement during the Ebola Virus Disease date = 2019-08-24 keywords = EBOV; EVD; Ebola; respiratory; virus summary = Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection. doi = 10.3390/v11090780 id = cord-002500-9p2n8tjx author = Lambe, Teresa title = A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? date = 2017-05-26 keywords = EBOV; EVD; Ebola; MVA; vaccine summary = The other vaccine modality being assessed as an Ebola vaccine candidate is the recombinant vesicular stomatitis virus encoding EBOV glycoprotein (rVSV-ZEBOV), which is an attenuated replication-competent viral vector. In the absence of any gold standard for measuring humoral immunity against Ebola virus, a wide variety of assays were used to evaluate antibody responses to vaccines during the recent EVD outbreak. Many of the other binding assays used in these Phase I trials correlate strongly and, in particular, it is useful that the standardized glycoprotein ELISA and pseudotyped lentivirus assays each correlate strongly with neutralizing titres against live Ebola virus as these assays avoid the need to work at high containment levels, but may be used to indicate the presence of antibodies with neutralizing activity. In a pre-clinical NHP model, IgG responses after immunization with AdHu5-based Ebola virus vaccines were measured using an ELISA against GP, where 100% protection against a lethal challenge was predicted by titres of 3700 or greater, while a titre of around 2000 predicted 85% survival. doi = 10.1098/rstb.2016.0295 id = cord-350565-mejd7blb author = Lewnard, Joseph A title = Emerging Challenges and Opportunities in Infectious Disease Epidemiology date = 2019-03-16 keywords = EBOV; Ebola; United; disease; study; vaccine summary = We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. Although serosurveys have bolstered recent efforts to understand the geographic range and clinical spectrum of EBOV and Zika virus infections (47, 48) , the enhancement of dengue hemorrhagic fever risk by prior exposure (49) , and the role of immunologic history in influenza susceptibility and vaccine response (50) , there remain few examples of public health programs undertaking serological studies for routine surveillance, at least in civilian populations (51) . doi = 10.1093/aje/kwy264 id = cord-276437-5gkdotvt author = Liu, William J. title = Intra-host Ebola viral adaption during human infection date = 2019-02-20 keywords = EBOV; Ebola; TNC summary = EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Recent studies also showed that, during the epidemic, the EBOV isolates from early in the outbreak with amino acid substitutions in the GP protein possessed increased tropism for human cells, indicating human adaptation of Ebola virus during human-to-human transmission [19] [20] [21] . In a single patient, genome sequences obtained from samples during earlier stages of the acute infection phase possessed Ts at the 13 TNC positions, whereas Cs were found from samples collected during the recovery process. Our data indicate that short stretches of TNC substitutions are part of the convergent evolution during the infection process of EVD patients, shedding light on the dynamic intra-host genomic variation of EBOV during the 2013-2016 epidemic. doi = 10.1016/j.bsheal.2019.02.001 id = cord-274377-57zy6unz author = Long, Jason title = Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry date = 2015-02-10 keywords = EBOV; ESOM; GALV summary = To this end we re-examined the anti-viral properties of CQ, and show here that it inhibited the pH-dependent endosomal entry of a pseudotyped virus (PV) bearing EBOV glycoproteins, in the same way as did the potent and specific vacuolar-ATPase (vATPase) inhibitor bafilyomycin A1 (BafA1) (a non-medical laboratory compound). We also show that licensed and widely used proton pump inhibitors (PPIs) for treatment of gastric acid reflux, omeprazole (OM) and esomeprazole (ESOM), inhibited PV EBOV entry, likely by their off-target inhibitory activity on endosomal vATPase. In this instance, a ''fusion inhibitor'' could target the host cell machinery preventing acidification of the endosome, working to inhibit virus entry of several different viruses. Given the volume of research suggesting these off target effects depend on an ability to affect intracellular pH, we hypothesised that these drugs would, like CQ and BafA1, inhibit EBOV, MARV and influenza virus pH dependent entry. doi = 10.12688/f1000research.6085.2 id = cord-293481-bmfj50fb author = Malin, Jakob J. title = Remdesivir against COVID-19 and Other Viral Diseases date = 2020-10-14 keywords = COVID-19; EBOV; MERS; RNA; SARS; remdesivir summary = Remdesivir or GS-5734 is a prodrug of a nucleoside analog with direct antiviral activity against several single-stranded RNA viruses, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, preliminary data from a randomized placebo-controlled clinical trial showed that remdesivir reduces the time to recovery in patients with COVID-19 (5) , leading to an emergency-use authorization (EUA) by the U.S. Food and Drug Administration (FDA) only 2 days after the first press release from the National Institute of Allergy and Infectious Diseases (NIAID) (6) . There were strong arguments for the antiviral effect of remdesivir against coronaviruses emerging from multiple cell-based in vitro models, including primary human airway epithelial (HAE) cell cultures (25) , and, for MERS-CoV, from a mouse model of pulmonary infection (28) . After the outbreak of SARS-CoV-2 in January 2020, remdesivir was rapidly tested in a Vero E6 cell-based model that made use of direct viral quantification by rtPCR along with the antimalaria and immune-modulating drug chloroquine and known antivirals such as ribavirin and penciclovir. doi = 10.1128/cmr.00162-20 id = cord-294342-7ycgd0h7 author = Markosyan, Ruben M. title = Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date = 2016-01-05 keywords = EBOV; Fig; NPC1; cell summary = On the question of low pH, we found that activation of cathepsins by acidity is the sole cause for augmentation of fusion: if EBOV GP on the cell surface is artificially cleaved by thermolysin in the presence of cathepsin inhibitors, the extent of fusion is independent of pH. We used thermolysin-treated effector cells to maximize cleavage of EBOV GP and found that adding CPZ either 30, 45, or 60 min after reneutralization did not induce any dye spread above that already observed, strongly indicating that a negligible percentage of cells were hemifused, but not fused, at any given time. The extent of fusion was greater when the inhibitor was not added (control): this indicates that delivery to the cell surface of EBOV GP cleaved by endosomal cathepsin (subsequent to thermolysin treatment) significantly contributes to fusion. doi = 10.1371/journal.ppat.1005373 id = cord-300133-yc2wxgid author = Martínez, Miguel J. title = Ebola Virus Infection: Overview and Update on Prevention and Treatment date = 2015-09-12 keywords = EBOV; EVD; Ebola; virus summary = In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Over the past 17 months, the West Africa EVD outbreak has provided an important opportunity to consider use of and evaluate several therapeutic and prophylactic agents (e.g., vaccines) to determine their safety and efficacy [5, 6] . FGI-103, FGI-104, and FGI-106 are a group of broad-spectrum antiviral agents that inhibit viral replication in a dose-dependent manner among multiple and genetically distinct viruses including EBOV, bunyaviruses, dengue virus, Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an emprical treatment during outbreaks doi = 10.1007/s40121-015-0079-5 id = cord-288734-xinkqs6u author = Muñoz-Fontela, César title = Ebola Virus Disease in Humans: Pathophysiology and Immunity date = 2017-03-30 keywords = EBOV; EVD; Ebola; Virus summary = Discovered in 1976 during the first documented outbreak of Ebola virus disease (EVD) in the town of Yambuku in northern Zaire (today Democratic Republic of the Congo), EBOV has since caused sporadic human disease outbreaks of varying magnitude in Equatorial African countries (Sanchez et al. Antigen-presenting cells are a putative initial target of EBOV infection and previous research in animal models of disease has indicated that dendritic cells (DCs) and macrophages are early and preferred targets of EBOV and support virus replication (Geisbert et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study Sequence-based human leukocyte antigen-B typing of patients infected with Ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes doi = 10.1007/82_2017_11 id = cord-279152-yh7x7w2q author = Ndungo, Esther title = A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles date = 2016-03-30 keywords = EBOV; NPC1 summary = Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. We also found that NPC1 could influence the cellular host range of filoviruses-human NPC1 conferred susceptibility to filovirus entry and infection when expressed in the nonpermissive reptilian cell line VH-2, derived from a Russell''s viper (Daboia russellii) (22) . These findings provide additional evidence that NPC1-encoded residue 503 influences the cellular host range of EBOV at the level of virus-receptor recognition and raise the possibility that sequence differences at this position influence the susceptibility of reptiles to filovirus infection in nature. doi = 10.1128/msphere.00007-16 id = cord-002185-oz7hras7 author = Nelson, Elizabeth A. title = Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date = 2016-08-02 keywords = EBOV; Ebola; VLP; figure summary = In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the doi = 10.3390/v8080206 id = cord-355737-o0y4rn0z author = Ng, Melinda title = Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats date = 2015-12-23 keywords = EBOV; Ebola; NPC1; african; bat; figure summary = To assess whether the EBOV infection defect in the African straw-colored fruit bat cells occurs at the viral entry step, we exposed an expanded panel of kidney fibroblast cell lines from four African pteropodids to VSV pseudotypes bearing GP spikes (VSV-GP) from seven filoviruses, including two non-African viruses, Reston virus (RESTV) and Lloviu virus (LLOV) ( Figure 1D ). Like the infection defect in African straw-colored fruit bat cells, this receptor binding defect was selective for EBOV GP, since GPs derived from MARV and the European filovirus, LLOV (Ng et al., 2014) , bound equivalently to all four pteropodid domain Cs ( Figure 4A ). . We conclude that a species-specific defect in virus-receptor interaction, caused by a single amino acid residue change in EhNPC1 relative to other, permissive African pteropodid NPC1 orthologs, reduces EBOV infection in African straw-colored fruit bat cells. doi = 10.7554/elife.11785 id = cord-350083-kldu8q8x author = Oany, Arafat Rahman title = Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach date = 2015-08-08 keywords = EBOV; Ebola; MHC; RNA summary = title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach doi = 10.1186/s40203-015-0011-4 id = cord-267941-nrluar4e author = Park, Eun-Mee title = Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells date = 2018-08-23 keywords = EBOV; Ebola summary = In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. In a previous study, VP2/6 double-layered rotavirus-like particles containing Wa capsid protein were produced in S2 cells transformed with a bicistronic expression system consisting of encephalomyocarditis virus (EMCV)-derived internal ribosomal entry site (IRES) element (Lee et al., 2011) . As shown in Fig. 1A , we confirmed that Ebola viral proteins were efficiently expressed in EBOV Makona-transfected S2 cells. Collectively, our findings suggested that the eVLPs produced by the S2 cell system in this study may be useful for the development of efficient VLP-based vaccines against EBOV. doi = 10.1016/j.jviromet.2018.08.016 id = cord-003859-k8wfyj9b author = Paweska, Janusz T. title = Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date = 2019-07-24 keywords = EBOV; ELISA; Ebola summary = title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans. doi = 10.3390/v11080678 id = cord-004335-bw3tziup author = Perez-Zsolt, Daniel title = When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date = 2019-12-19 keywords = EBOV; Ebola; HIV-1; Siglec-1 summary = Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. Thus, infection with viruses such as HIV-1 or EBOV tightly upregulates Siglec-1 expression on APCs, as they directly trigger or indirectly promote the release of type I IFNs via immune activating factors (Figure 1 ). Thus, HIV-1 and EBOV infections trigger an immune activation state that upregulates Siglec-1 expression on DCs, a situation that might favor early viral dissemination events in an otherwise antiviral environment [80] . doi = 10.3390/v12010008 id = cord-002935-jq1xumrh author = Postnikova, Elena title = Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date = 2018-03-22 keywords = EBOV; Ebola; MOI; Vero summary = Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. The CELIA was compared to the fluorescent assay (detected by regular plate reader or the HCI system) by testing the efficacy of toremifene citrate against EBOV infection in Huh 7 cells with a range of MOIs (0.1, 0.3, 1, and 3 ) at three different time points (24, 48 and 72 hpi) . The established CELIA was used to compare anti-EBOV activity of toremifene citrate in 3 different cell types, Vero E6, Huh 7 and MDMs using an MOI of 0.5 and a time point of 48 h (Fig 7) . doi = 10.1371/journal.pone.0194880 id = cord-303647-c4umbcvn author = Reed, Patricia E. title = A New Approach for Monitoring Ebolavirus in Wild Great Apes date = 2014-09-18 keywords = EBOV; Ebola; ape; sample summary = CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. In zone A, 20 gorilla fecal samples were opportunistically collected while following habituated gorillas roughly 2 and 3 years after ebolavirus infection was confirmed in ape carcasses at that site using a combination of RT-PCR, immunohistochemistry and antigen capture [5, 9] . All human EVD outbreaks that had previously occurred in our sampling zone study are thought to be the result of handling infected wild animal carcasses, including gorillas [13] . This study represents the first time that ebolavirus antibodies have been detected in wild great ape fecal samples, and carries important implications for the future management and survival of these primates. doi = 10.1371/journal.pntd.0003143 id = cord-305653-f9vqn96o author = Schmidt, Rebecca title = Generation of therapeutic antisera for emerging viral infections date = 2018-10-05 keywords = EBOV; Ebola; VSVΔG summary = Animal-origin purified IgG 27 and IgG fragment preparations are still routinely used as antivenoms, and even though immunization of horses with inactivated EBOV failed to yield effective therapeutic antisera, 28 equine hyperimmune sera produced using EBOV virus-like particles (VLPs) conferred protection against lethal challenge in rodents. To determine the importance of this aspect for the induction of functional antibodies, we compared adjuvanted EBOV VLPs with vector vaccines based on the replication-deficient modified vaccinia Ankara virus (MVA) that expresses either the GP protein of the Zaire EBOV Guéckédou strain alone or in combination with VP40 (unpublished data), and the replication-competent VSVΔG/EBOV-GP. Even though the neutralizing antibodies were again only detected after the first boost in the group immunized with adjuvanted EBOV VLPs, titers ultimately reached levels around 100 (Fig. 2b) , illustrating that de novo protein expression is not required for efficient induction of functional antibodies. doi = 10.1038/s41541-018-0082-4 id = cord-102206-mb0qcd0b author = Seymour, Elif title = Configurable Digital Virus Counter on Robust Universal DNA Chips date = 2020-10-22 keywords = EBOV; IRIS; dna summary = Here, we demonstrate real-time multiplexed virus detection by applying DNA-directed antibody immobilization technique to a single-particle interferometric reflectance imaging sensor (SP-IRIS). We also show that this method can be modified to produce a single-step, homogeneous assay format by mixing the antibody-DNA conjugates with the virus sample in solution phase prior to flowing in the microfluidic cartridge, eliminating the antibody immobilization step. 16 SP-IRIS has been utilized for detecting viruses in complex media using antibody microarrays by imaging chips both dry (dried after sample incubation and wash steps) and in liquid using disposable microfluidic cartridges. To demonstrate the feasibility of using the homogeneous assay in combination with the passive flow cartridge and to compare its performance to the directly immobilized antibody assay, an SP-IRIS chip was printed with anti-EBOV mAb, A'' probe, and a negative DNA sequence, and washed as described previously. doi = 10.1101/2020.10.22.350579 id = cord-003779-5yhoiv76 author = Singleton, Courtney D. title = Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry date = 2019-07-17 keywords = EBOV; Ebola; FPS; Fig; GP2; I49 summary = Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. The computational screening resulted in the prioritization and purchase of 165 compounds for experimental characterization, which led to 11 hits that inhibit viral entry in both EBOV-GP-pseudotyped virus and EBOV transcription-and replicationcompetent virus-like particle (trVLP) systems. Molecular dynamics (MD) simulations in conjunction with genome analysis identified 7 highly conserved residues across different Ebola virus strains (E564.A, A568.A, L571.A, F572.A, T566.C, L569.C, and L573.C) that contribute a majority of the favorable interactions between the compounds and GP2. doi = 10.1128/jvi.00676-19 id = cord-318587-ewvnkdr2 author = Steeds, Kimberley title = Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date = 2020-08-31 keywords = EBOV; HIV-1; VSV summary = We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). doi = 10.1038/s41598-020-71225-1 id = cord-337998-08tknscm author = Sztuba-Solinska, Joanna title = A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8 date = 2016-11-16 keywords = EBOV; HSPA8; RNA; a30u; figure summary = Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. 3E-5E-GFP minigenome RNA secondary structure and host protein interactions were examined using selective 2 -hydroxyl acylation analyzed by primer extension (SHAPE) (38, 39) , antisense-interfered SHAPE (aiSHAPE) (40) , electrophoretic mobility shift assays (EMSA), siRNA, and mutational analysis, using both the 3E-5E-GFP minigenome system and EBOV reverse genetics. The secondary structure of the EBOV 3E-5E-GFP minigenome RNA predicted by RNAstructure software version 5.7 (48) and chemical probing data from SHAPE were used to generate 10 three-dimensional (3D) models for the trailer-to-leader panhandle interaction in the wt-EBOV genome and variants, A30U and A26U/A30U, using open-source RNAComposer, version 1.0 (http://rnacomposer.cs.put.poznan.pl/). doi = 10.1093/nar/gkw825 id = cord-017811-w38mbvdw author = Volchkov, Viktor title = Proteolytic Processing of Filovirus Glycoproteins date = 2018-02-16 keywords = EBOV; Ebola summary = After entering cells by macropinocytosis, the glycan cap and the mucin-like domain are removed from GP1 by endosomal cathepsins B and L exposing the binding site for the Niemann-Pick C1 receptor. The surface glycoprotein of MARV is proteolytically processed in a similar way as that of EBOV; two precursor molecules and mature GP1,2 consisting of the disulfide-linked cleavage products GP1 and GP2 were identified in cells expressing MARV GP and in Marburg virions (Volchkov et al. Like EBOV, MARV enters cells by macropinocytosis and endosomal fusion, but there are some differences in the structure and in endosomal processing of the glycoproteins. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression Endoproteolytic processing of the Ebola virus envelope glycoprotein: cleavage is not required for function doi = 10.1007/978-3-319-75474-1_5 id = cord-272576-ez731lif author = Wada, Yoshiko title = Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date = 2016-11-03 keywords = EBOV; Fig; RNA summary = To face the world-wide threats caused by zoonotic RNA viruses, which suddenly cause serious outbreaks by invasion from nonhuman hosts and mutate rapidly, we must understand the molecular evolutionary changes in their genome sequences extensively by innovating various technologies, including those used in big data analyses, e.g., large-scale word count. The present time-series analysis on influenza A genomes showed that the 20-mers exhibiting the most evident directional changes observed in common for three different subtypes corresponded to several influenza A siRNAs, which were experimentally validated. The present study focused on time-series changes, but not on data variations caused largely by random mutations and sequencing uncertainty, and therefore, average characteristics of strains isolated in a similar period were analyzed, summing up the sequences isolated in one month and calculating an averaged mononucleotide composition for each month (Fig. 1b) . doi = 10.1038/srep36197 id = cord-346267-l08ld2cy author = Wertheim, Joel O. title = Purifying Selection Can Obscure the Ancient Age of Viral Lineages date = 2011-06-24 keywords = EBOV; GTR; RNA summary = Over longer periods of evolutionary time (i.e., along long internal branches on a phylogenetic tree), evidence of evolution at the nucleotide level could be lost, which could bias tMRCA estimates towards younger dates (i.e., underestimate the length of these branches). The results presented here demonstrate that not accounting for purifying selection may bias tMRCA estimation in RNA viruses towards more recent dates, and a degree of correction can be realized by employing more realistic codon-based substitution models, capable of partially accounting for the biasing effect of purifying selection. Using BMCMC analysis, we inferred the substitution rate and root age under a standard nucleotide substitution model (GTR + Γ 4 ) for each of our three viral data sets: MeV/RPV/PPRV nucleoprotein, EBOV glycoprotein, and AIV neuraminidase (table 1) . The nucleotide substitution model (GTR + Γ 4 ) underestimated the length of branches simulated under empirical (IFEL) selection regimes inferred from the three viral data sets ( fig. doi = 10.1093/molbev/msr170 id = cord-284791-bgodmbru author = Whitworth, Carrie title = Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate date = 2020-08-18 keywords = EBOV; Ebola; SARS summary = The persistence of phi 6 was evaluated as a surrogate for Ebola virus (EBOV) and coronaviruses on porous and nonporous hospital surfaces. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses. This study evaluated the persistence of phi 6 in the presence of artificial test soil (ATS) as a potential surrogate for EBOV or coronaviruses at two absolute humidity (AH) conditions on four potential fomites: nonporous stainless steel (SS) and plastic (PL) and two types of porous hospital curtain fabrics. found that the Phi 6 was shown here in the current study to be a conservative surrogate for EBOV in a laboratory-simulated Western hospital room condition of 3.0 g/m 3 AH, persisting longer than the Makona-C05 variant (AH ϭ 3.3 g/m 3 ), with decay rates of 0.06 log 10 /d and 0.79 log 10 /h, respectively (Table 1 ). doi = 10.1128/aem.01482-20 id = cord-296517-414grqif author = Wong, Gary title = MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease date = 2015-10-14 keywords = EBOV; MERS; SARS summary = In September 2012, Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged as a novel virus that can result in severe respiratory disease with renal failure, with a case fatality rate of up to 38%. Notably, between May and July 2015, an outbreak of MERS-CoV centered in South Korea killed 36 people out of 186 confirmed cases (Promedmail.org, 2015) , with thousands quarantined as health authorities attempted to control virus spread. The 2015 MERS-CoV outbreak in South Korea began from an imported case, a 68-year-old male with a recent travel history to several Middle Eastern countries, including Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar. Thus, the MERS-CoV outbreak in South Korea was driven primarily by three infected individuals, and approximately 75% of cases can be traced back to three super-spreaders who have each infected a disproportionately high number of contacts ( Figure 1A ). doi = 10.1016/j.chom.2015.09.013 id = cord-330647-w1bpeqzg author = Wong, Samson Sai-Yin title = Ebola virus disease in nonendemic countries date = 2015-05-31 keywords = EBOV; EVD; Ebola; FHF; Marburg; fever; virus summary = The largest outbreak of Ebola virus disease (EVD) in history has renewed interest in filoviruses and has provided an unprecedented impetus to the development of new therapeutics and vaccines for this highly lethal infection. Nucleic acid amplification is the diagnostic test of choice because of its high sensitivity (especially in the early phase of illness); its ability to differentiate between different agents of viral hemorrhagic fever; and its relatively lower biohazard, if the viruses are appropriately inactivated; and because antigen and antibody assays are often unavailable in laboratories in nonendemic countries. 119e123 Animal studies also demonstrate the efficacy of favipiravir in the treatment of Junín virus, arenavirus, and EBOV hemorrhagic fevers, and the drug was used to treat human EVD in the 2014 West African epidemic. doi = 10.1016/j.jfma.2015.01.012 id = cord-322748-a5131tv9 author = Yates, Mary K. title = Flex-nucleoside analogues – Novel therapeutics against filoviruses date = 2017-06-15 keywords = EBOV; virus summary = Most recently GS-5734, a monophosphoramidate prodrug adenosine analogue which targets EBOV RNA-dependent RNA polymerase (RdRp), exhibited very potent activity against both EBOV and MARV, 17, 18 further demonstrating the potential for finding effective nucleoside inhibitors of filoviruses. After the successful synthesis of the three Flex-analogues 1, 2, and 3, the compounds were screened against a panel of filoviruses including EBOV, MARV, and SUDV, as well as other hemorrhagic fever viruses such as Lassa and Rift Valley Fever. The second series of assays utilized Huh7 cells infected with recombinant reporter EBOV, Lassa, and Rift Valley Fever viruses. Within this study we found that both compounds 1 and 3 exhibited antiviral activity against a recombinant reporter EBOV in Huh7 cells, though surprisingly the McGuigan prodrug was 10-fold less potent (EC 50 = 2.2 ± 0.3 lM and 27.2 ± 2.2 lM respectively). doi = 10.1016/j.bmcl.2017.04.069 id = cord-297082-2rhoffx2 author = Yu, Changqing title = MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date = 2020-09-15 keywords = EBOV; Fig; march8 summary = Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. As a control, serine incorporator 5 (SERINC5) protein In addition, FLAG-tagged furin was expressed with HA-tagged human MARCH8 and GPΔMLD in 293T cells. In addition, when the furin-VN/GP-VC pair was expressed with MARCH8, their colocalization was also detected (Fig. 2C ), confirming that these three molecules form a complex in live cells. MARCH8 proteins from different species strongly increased GP 1 and GP 1 ΔMLD expression in cells but completely blocked their secretions (Fig. 7C, lanes 1 to 8) . doi = 10.1128/mbio.01882-20 id = cord-002676-zwkl1ywk author = Yu, Dong-Shan title = The lifecycle of the Ebola virus in host cells date = 2017-06-15 keywords = EBOV; Ebola; RNA; VP40 summary = However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. Then, the Tyro3 protein kinase (TAM) family, including Axl, Dtk, and Mer, which widely expressed in many cell types, span the plasma membrane and contain intracellular tyrosine kinase domains, are facilitate EBOV GP-dependent attachment [39, 40] . In addition, folate receptor-α (FR-α) was reported to be a co-receptor in binding cells that expressed MARV or EBOV GP, mediated syncytia formation triggered by GP, and facilitated cellular entry of the virus [28] . After the virus has been internalized into the endosome, fusion induced by cleaved GP is fundamentally independent of pH, which indicated an unidentified host cell factor critical for filovirus entry is sensitive to an acidic pH [56] . Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus doi = 10.18632/oncotarget.18498 id = cord-102763-tc1z0nm9 author = Zhang, Yuan title = IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability date = 2020-05-21 keywords = EBOV; Ebola summary = Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa. To obtain high titer EBOV NAbs, 5-month-old laying hens were vaccinated with five different 124 immunogens, including 10 3 or 10 4 TCID 50 VSVΔ G/EBOVGP, 100 μ g rEBOVGP, 100 μ g 125 pCAGGS/EBOVGP, 10 μg EBOV-VLP, and 10 11 virus particles (vp) Ad5/EBOVGP (Fig 2a) . Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody doi = 10.1101/2020.05.21.108159 id = cord-002013-rb9xdzro author = Zheng, Xuexing title = Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date = 2016-04-12 keywords = EBOV; Ebola; PBS; antisera summary = To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. doi = 10.1038/srep24179