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      Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

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          Abstract

          Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed.

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          Most cited references168

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          Drugs for bad bugs: confronting the challenges of antibacterial discovery.

          The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
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            Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.

            Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)-derived cholesterol. By positional cloning methods, a gene (NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking. The 1278-amino acid NPC1 protein has sequence similarity to the morphogen receptor PATCHED and the putative sterol-sensing regions of SREBP cleavage-activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase.
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              Parainfluenza viruses.

              Human parainfluenza viruses (HPIV) were first discovered in the late 1950s. Over the last decade, considerable knowledge about their molecular structure and function has been accumulated. This has led to significant changes in both the nomenclature and taxonomic relationships of these viruses. HPIV is genetically and antigenically divided into types 1 to 4. Further major subtypes of HPIV-4 (A and B) and subgroups/genotypes of HPIV-1 and HPIV-3 have been described. HPIV-1 to HPIV-3 are major causes of lower respiratory infections in infants, young children, the immunocompromised, the chronically ill, and the elderly. Each subtype can cause somewhat unique clinical diseases in different hosts. HPIV are enveloped and of medium size (150 to 250 nm), and their RNA genome is in the negative sense. These viruses belong to the Paramyxoviridae family, one of the largest and most rapidly growing groups of viruses causing significant human and veterinary disease. HPIV are closely related to recently discovered megamyxoviruses (Hendra and Nipah viruses) and metapneumovirus.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                21 September 2012
                September 2012
                : 4
                : 9
                : 1619-1650
                Affiliations
                [1 ]United States Army Medical Research Institute of Infectious Diseases, Division of Virology, 1425 Porter Street, Frederick, MD 21702, USA; Email: brian.m.friedrich.ctr@ 123456us.army.mil (B.M.F.); john.c.trefry.ctr@ 123456us.army.mil (J.C.T.); julia.biggins@ 123456us.army.mil (J.E.B.); anna.honko@ 123456us.army.mil (A.N.H.); darci.smith1@ 123456us.army.mil (D.R.S.)
                [2 ]United States Food and Drug Administration (FDA), Medical Science Countermeasures Initiative (McMi), 10903 New Hampshire Avenue, Silver Spring, MD 20901, USA; Email: lisa.hensley@ 123456fda.hhs.gov (L.E.H.)
                Author notes
                [† ]

                These authors contributed equally to this work.

                [* ] Author to whom correspondence should be addressed; Email: Gene.olinger@ 123456us.army.mil (G.G.O.); Tel.: +1-301-619-8581; +1-301-619-2290.
                Article
                viruses-04-01619
                10.3390/v4091619
                3499823
                23170176
                eddf4ca8-cd10-4c65-843c-ef219790ec75
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 20 July 2012
                : 31 August 2012
                : 04 September 2012
                Categories
                Review

                Microbiology & Virology
                animal models,ebola,filovirus,marburg virus,vaccines,post-exposure treatments,marburgvirus,ebolavirus,clinical trials,non-human primates

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