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https://www.readbyqxmd.com/read/28640812/challenges-in-preparing-and-implementing-a-clinical-trial-at-field-level-in-an-ebola-emergency-a-case-study-in-guinea-west-africa
#1
Sara Carazo Perez, Elin Folkesson, Xavier Anglaret, Abdoul-Habib Beavogui, Emmanuel Berbain, Alseny-Modet Camara, Evelyn Depoortere, Annabelle Lefevre, Piet Maes, Kristian Nødtvedt Malme, Jean-Marie Denis Malvy, Sien Ombelet, Geertrui Poelaert, Daouda Sissoko, Alexis Tounkara, Pierre Trbovic, Pascal Piguet, Annick Antierens
During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28596841/targeting-endosomal-acidification-by-chloroquine-analogs-as-a-promising-strategy-for-the-treatment-of-emerging-viral-diseases
#2
REVIEW
Md Abdul Alim Al-Bari
Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28580138/plasma-membrane-association-facilitates-conformational-changes-in-the-marburg-virus-protein-vp40-dimer
#3
Nisha Bhattarai, Jeevan B Gc, Bernard S Gerstman, Robert V Stahelin, Prem P Chapagain
Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch...
April 26, 2017: RSC Advances
https://www.readbyqxmd.com/read/28576573/rapid-development-of-vaccines-against-emerging-pathogens-the-replication-deficient-simian-adenovirus-platform-technology
#4
Sarah C Gilbert, George M Warimwe
Despite the fact that there had been multiple small outbreaks of Ebola Virus Disease, when a large outbreak occurred in 2014 there were no vaccines or drugs available for use. Clinical development of multiple candidate vaccines was then initiated in parallel with attempts to contain the outbreak but only one vaccine was eventually tested in a phase III trial. In order to be better prepared for future outbreaks of known human pathogens, platform technologies to accelerate vaccine development should be employed, allowing vaccine developers to take advantage of detailed knowledge of the vaccine platform and facilitating rapid progress to clinical trials and eventually to vaccine stockpiles...
May 30, 2017: Vaccine
https://www.readbyqxmd.com/read/28574091/macrocyclic-peptide-inhibitors-for-the-protein-protein-interaction-of-zaire-ebola-virus-protein-24-and-karyopherin-alpha-5
#5
Xiao Song, Lu-Yi Lu, Toby Passioura, Hiroaki Suga
Ebola virus infection leads to severe hemorrhagic fever in human and non-human primates with an average case fatality rate of 50%. To date, numerous potential therapies are in development, but FDA-approved drugs or vaccines are yet unavailable. Ebola viral protein 24 (VP24) is a multifunctional protein that plays critical roles in the pathogenesis of Ebola virus infection, e.g. innate immune suppression by blocking the interaction between KPNA and PY-STAT1. Here we report macrocyclic peptide inhibitors of the VP24-KPNA5 protein-protein interaction (PPI) by means of the RaPID (Random non-standard Peptides Integrated Discovery) system...
June 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28542609/potent-and-selective-inhibition-of-pathogenic-viruses-by-engineered-ubiquitin-variants
#6
Wei Zhang, Ben A Bailey-Elkin, Robert C M Knaap, Baldeep Khare, Tim J Dalebout, Garrett G Johnson, Puck B van Kasteren, Nigel J McLeish, Jun Gu, Wenguang He, Marjolein Kikkert, Brian L Mark, Sachdev S Sidhu
The recent Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola and Zika virus outbreaks exemplify the continued threat of (re-)emerging viruses to human health, and our inability to rapidly develop effective therapeutic countermeasures. Many viruses, including MERS-CoV and the Crimean-Congo hemorrhagic fever virus (CCHFV) encode deubiquitinating (DUB) enzymes that are critical for viral replication and pathogenicity. They bind and remove ubiquitin (Ub) and interferon stimulated gene 15 (ISG15) from cellular proteins to suppress host antiviral innate immune responses...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28532397/a-systematic-review-of-factors-that-shape-implementation-of-mass-drug-administration-for-lymphatic-filariasis-in-sub-saharan-africa
#7
Adam Silumbwe, Joseph Mumba Zulu, Hikabasa Halwindi, Choolwe Jacobs, Jessy Zgambo, Rosalia Dambe, Mumbi Chola, Gershom Chongwe, Charles Michelo
BACKGROUND: Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities...
May 22, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28523851/identification-of-multiple-druggable-secondary-sites-by-fragment-screening-against-dc-sign
#8
Jonas Aretz, Hannes Baukmann, Elena Shanina, Jonas Hanske, Robert Wawrzinek, Viktor A Zapol'skii, Peter H Seeberger, Dieter E Kaufmann, Christoph Rademacher
DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using (19) F NMR spectroscopy and chemical fragment microarrays...
June 12, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#9
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28516937/ebola-outbreak-in-the-congo-tuberculosis-drug-resistance-in-russia-and-gm-mustard-seeds-in-india
#10
(no author information available yet)
No abstract text is available yet for this article.
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#11
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28462833/recent-progress-on-the-treatment-of-ebola-virus-disease-with-favipiravir-and-other-related-strategies
#12
Tao Zhang, Min Zhai, Jianbo Ji, Jian Zhang, Ye Tian, Xinyong Liu
Ebola virus is one of the most threatening pathogens with the mortality rate as high as 90% in the world. There are no licensed therapeutic drugs or preventive vaccines for Ebola hemorrhagic fever up to date. Favipiravir, a novel antiviral drug which was mainly used for the treatment of influenza, now has been demonstrated to have a curative effect in treating Ebola virus infection. In this review, we present an overview of recent progress on the treatment of Ebola virus disease with Favipiravir and describe its possible mechanism...
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28457226/commentary-restarting-ntd-programme-activities-after-the-ebola-outbreak-in-liberia
#13
Brent C Thomas, Karsor Kollie, Benjamin Koudou, Charles Mackenzie
It is widely known that the recent Ebola Virus Disease (EVD) in West Africa caused a serious disruption to the national health system, with many of ongoing disease focused programmes, such as mass drug administration (MDA) for onchocerciasis (ONC), lymphatic filariasis (LF) and schistosomiasis (SCH), being suspended or scaled-down. As these MDA programmes attempt to restart post-EVD it is important to understand the challenges that may be encountered. This commentary addresses the opinions of the major health sectors involved, as well as those of community members, regarding logistic needs and challenges faced as these important public health programmes consider restarting...
May 1, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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