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https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#1
Changchuan Yin, Stephen S-T Yau
Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28404864/longitudinal-peripheral-blood-transcriptional-analysis-of-a-patient-with-severe-ebola-virus-disease
#2
John C Kash, Kathie-Anne Walters, Jason Kindrachuk, David Baxter, Kelsey Scherler, Krisztina B Janosko, Rick D Adams, Andrew S Herbert, Rebekah M James, Spencer W Stonier, Matthew J Memoli, John M Dye, Richard T Davey, Daniel S Chertow, Jeffery K Taubenberger
The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#3
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28402862/cooperativity-enables-non-neutralizing-antibodies-to-neutralize-ebolavirus
#4
Katie A Howell, Jennifer M Brannan, Christopher Bryan, Andrew McNeal, Edgar Davidson, Hannah L Turner, Hong Vu, Sergey Shulenin, Shihua He, Ana Kuehne, Andrew S Herbert, Xiangguo Qiu, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, John M Dye, M Javad Aman
Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several "enabling pairs" of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC50 >1 μM) to exhibit potent neutralization (IC50 1-10 nM)...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28377530/topoisomerase-ii-inhibitors-induce-dna-damage-dependent-interferon-responses-circumventing-ebola-virus-immune-evasion
#5
Priya Luthra, Sebastian Aguirre, Benjamin C Yen, Colette A Pietzsch, Maria T Sanchez-Aparicio, Bersabeh Tigabu, Lorraine K Morlock, Adolfo García-Sastre, Daisy W Leung, Noelle S Williams, Ana Fernandez-Sesma, Alexander Bukreyev, Christopher F Basler
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28376850/depressive-symptoms-among-survivors-of-ebola-virus-disease-in-conakry-guinea-preliminary-results-of-the-postebogui-cohort
#6
Mamady Mory Keita, Bernard Taverne, Sékou Sy Savané, Laura March, Morifodé Doukoure, Mamadou Saliou Sow, Abdoulaye Touré, Jean François Etard, Moumié Barry, Eric Delaporte
BACKGROUND: The 2013-2016 West African Ebola outbreak infected 28,616 people and caused 11,310 deaths by 11 May 2016, across six countries. The outbreak has also resulted in the largest number of EVD survivors in history-over 17,000. Guinea was declared Ebola-free on 1 June 2016. Reports from the outbreak documented 3814 cases resulting in 2544 deaths and 1270 survivors. EVD survivors face various neuropsychological and psycho-affective alterations that have not been fully identified yet...
April 4, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28358050/antibody-dependent-cellular-cytotoxicity-inducing-antibodies-significantly-affect-the-post-exposure-treatment-of-ebola-virus-infection
#7
Qiang Liu, Changfa Fan, Qianqian Li, Shuya Zhou, Weijin Huang, Lan Wang, Chunyun Sun, Meng Wang, Xi Wu, Jian Ma, Baowen Li, Liangzhi Xie, Youchun Wang
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357917/the-ongoing-evolution-of-antibody-based-treatments-for-ebola-virus-infection
#8
Emelissa J Mendoza, Trina Racine, Gary P Kobinger
The 2014-2016 Ebola virus outbreak in West Africa was the deadliest in history, prompting the evaluation of various drug candidates, including antibody-based therapeutics for the treatment of Ebola hemorrhagic fever (EHF). Prior to 2014, only convalescent blood products from EHF survivors had been administered to newly infected individuals as a form of treatment. However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28351976/comparing-nonpharmaceutical-interventions-for-containing-emerging-epidemics
#9
Corey M Peak, Lauren M Childs, Yonatan H Grad, Caroline O Buckee
Strategies for containing an emerging infectious disease outbreak must be nonpharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these nonpharmaceutical strategies will depend on not only the effectiveness of isolation measures but also the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28299152/ebola-viral-disease-in-west-africa-a-threat-to-global-health-economy-and-political-stability
#10
Semeeh Akinwale Omoleke, Ibrahim Mohammed, Yauba Saidu
The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences...
August 17, 2016: Journal of Public Health in Africa
https://www.readbyqxmd.com/read/28277549/the-final-oral-ebola-vaccine-trial-on-captive-chimpanzees
#11
Peter D Walsh, Drishya Kurup, Dana L Hasselschwert, Christoph Wirblich, Jason E Goetzmann, Matthias J Schnell
Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28240606/anticancer-kinase-inhibitors-impair-intracellular-viral-trafficking-and-exert-broad-spectrum-antiviral-effects
#12
Elena Bekerman, Gregory Neveu, Ana Shulla, Jennifer Brannan, Szu-Yuan Pu, Stanley Wang, Fei Xiao, Rina Barouch-Bentov, Russell R Bakken, Roberto Mateo, Jennifer Govero, Claude M Nagamine, Michael S Diamond, Steven De Jonghe, Piet Herdewijn, John M Dye, Glenn Randall, Shirit Einav
Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28231247/favipiravir-pharmacokinetics-in-ebola-infected-patients-of-the-jiki-trial-reveals-concentrations-lower-than-targeted
#13
Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec, Géraldine Piorkowski, Sara Carazo, Mamoudou N Conde, Jean-Luc Gala, Joseph Akoi Bore, Caroline Carbonnelle, Frédéric Jacquot, Hervé Raoul, Denis Malvy, Xavier de Lamballerie, France Mentré
BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28225767/interferon-%C3%AE-1a-for-the-treatment-of-ebola-virus-disease-a-historically-controlled-single-arm-proof-of-concept-trial
#14
Mandy Kader Konde, Darren P Baker, Fode Amara Traore, Mamadou Saliou Sow, Alioune Camara, Alpha Amadou Barry, Doussou Mara, Abdoulaye Barry, Moussa Cone, Ibrahima Kaba, Amento Ablam Richard, Abdoul Habib Beavogui, Stephan Günther, Melania Pintilie, Eleanor N Fish
To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit...
2017: PloS One
https://www.readbyqxmd.com/read/28216179/the-17th-international-congress-on-infectious-diseases-workshop-on-developing-infection-prevention-and-control-resources-for-low-and-middle-income-countries
#15
Sangeeta Sastry, Nadia Masroor, Gonzalo Bearman, Rana Hajjeh, Alison Holmes, Ziad Memish, Britta Lassmann, Didier Pittet, Fiona Macnab, Rachel Kamau, Evelyn Wesangula, Paras Pokharel, Paul Brown, Frances Daily, Fatma Amer, Jaime Torres, Miguel O'Ryan, Revathi Gunturu, Andre Bulabula, Shaheen Mehtar
Hospital-acquired infections (HAIs) are a major concern to healthcare systems around the world. They are associated with significant morbidity and mortality, in addition to increased hospitalization costs. Recent outbreaks, including those caused by the Middle East respiratory syndrome coronavirus and Ebola virus, have highlighted the importance of infection control. Moreover, HAIs, especially those caused by multidrug-resistant Gram-negative rods, have become a top global priority. Although adequate approaches and guidelines have been in existence for many years and have often proven effective in some countries, the implementation of such approaches in low- and middle-income countries (LMICs) is often restricted due to limited resources and underdeveloped infrastructure...
February 16, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28160722/molecular-modeling-simulation-and-docking-study-of-ebola-virus-glycoprotein
#16
Nasir Ahmad, Aqsa Farman, Syed Lal Badshah, Ata Ur Rahman, Haroon Ur Rashid, Khalid Khan
Ebola virus (EBOV) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. In this study secreted glycoprotein (Q7T9E0) of Ebola virus was acquired from Uniprot. The formation of alpha helix and beta sheets of secondary structures were predicted through online servers. Higher flexibility and disordered regions of proteins were determined through RONN, GLOBPLOT and DISSEMBLE...
March 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28152588/a-sensitive-in-vitro-high-throughput-screen-to-identify-pan-filoviral-replication-inhibitors-targeting-the-vp35-np-interface
#17
Gai Liu, Peter J Nash, Britney Johnson, Colette Pietzsch, Ma Xenia G Ilagan, Alexander Bukreyev, Christopher F Basler, Terry L Bowlin, Donald T Moir, Daisy W Leung, Gaya K Amarasinghe
The 2014 Ebola outbreak in West Africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting Ebola virus (EBOV). Within the EBOV replication complex, the interaction between polymerase cofactor, viral protein 35 (VP35), and nucleoprotein (NP) is critical for viral RNA synthesis. We recently identified a peptide at the N-terminus of VP35 (termed NPBP) that is sufficient for interaction with NP and suppresses EBOV replication, suggesting that the NPBP binding pocket can serve as a potential drug target...
March 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28117364/selective-inhibition-of-ebola-entry-with-selective-estrogen-receptor-modulators-by-disrupting-the-endolysosomal-calcium
#18
Hanlu Fan, Xiaohong Du, Jingyuan Zhang, Han Zheng, Xiaohui Lu, Qihui Wu, Haifeng Li, Han Wang, Yi Shi, George Gao, Zhuan Zhou, Dun-Xian Tan, Xiangdong Li
The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095824/community-based-health-care-is-an-essential-component-of-a-resilient-health-system-evidence-from-ebola-outbreak-in-liberia
#19
Kendra Siekmans, Salim Sohani, Tamba Boima, Florence Koffa, Luay Basil, Saïd Laaziz
BACKGROUND: Trained community health workers (CHW) enhance access to essential primary health care services in contexts where the health system lacks capacity to adequately deliver them. In Liberia, the Ebola outbreak further disrupted health system function. The objective of this study is to examine the value of a community-based health system in ensuring continued treatment of child illnesses during the outbreak and the role that CHWs had in Ebola prevention activities. METHODS: A descriptive observational study design used mixed methods to collect data from CHWs (structured survey, n = 60; focus group discussions, n = 16), government health facility workers and project staff...
January 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28095476/a-systematic-review-of-ebola-treatment-trials-to-assess-the-extent-to-which-they-adhere-to-ethical-guidelines
#20
Thomas Richardson, Andrew McDonald Johnston, Heather Draper
BACKGROUND: Objective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct. Design: Systematic review and narrative analysis. METHODS AND FINDINGS: Data sources: MEDBASE and EMBASE databases were searched using a specific search strategy. The Cochrane database for systematic reviews, the PROSPERO database and trial registries were examined. A grey literature search and citation search were also carried out...
2017: PloS One
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