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  1 / 1168 MEDLINE  
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[PMID]:29030319
[Au] Autor:Dutta S; Celestine MJ; Khanal S; Huddleston A; Simms C; Arca JF; Mitra A; Heller L; Kraj PJ; Ledizet M; Anderson JF; Neelakanta G; Holder AA; Sultana H
[Ad] Endereço:Department of Biological Sciences, Old Dominion University, Norfolk, VA, USA.
[Ti] Título:Coordination of different ligands to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes.
[So] Source:Biochim Biophys Acta;1862(1):40-50, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Trace elements such as copper and cobalt have been associated with virus-host interactions. However, studies to show the effect of conjugation of copper(II) or cobalt(III) metal centers to thiosemicarbazone ligand(s) derived from either food additives or mosquito repellent such as 2-acetylethiazole or citral, respectively, on Zika virus (ZIKV) or dengue virus (serotype 2; DENV2) infections have not been explored. In this study, we show that four compounds comprising of thiosemicarbazone ligand derived from 2-acetylethiazole viz., (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide (acetylethTSC) (compound 1), a copper(II) complex with acetylethTSC as a ligand (compound 2), a thiosemicarbazone ligand-derived from citral (compound 3) and a cobalt(III) complex with a citral-thiosemicarbazone ligand (compound 4) increased DENV2 and ZIKV replication in both mosquito C6/36 cells and human keratinocytes (HaCaT cells). Treatment of both cell lines with compounds 2 or 4 showed increased dengue viral titers at all three tested doses. Enhanced dengue viral plaque formation was also noted at the tested dose of 100µM, suggesting higher production of infectious viral particles. Treatment with the compounds 2 or 4 enhanced ZIKV and DENV2 RNA levels in HeLa cell line and primary cultures of mouse bone marrow derived dendritic cells. Also, pre- or post treatments with conjugated compounds 2 or 4 showed higher loads of ZIKV or DENV2 envelope (E) protein in HaCaT cells. No changes in loads of E-protein were found in ZIKV-infected C6/36 cells, when compounds were treated after infection. In addition, we tested bis(1,10-phenanthroline)copper(II) chloride ([Cu(phen) ]Cl , (compound 5) and tris(1,10-phenanthroline)cobalt(III) chloride ([Co(phen) ]Cl , (compound 6) that also showed enhanced DENV2 loads. Also, we found that copper(II) chloride dehydrate (CuCl ·2H O) or cobalt(II) chloride hexahydrate (CoCl ·6H O) alone had no effects as "free" cations. Taken together, these findings suggest that use of Cu(II) or Co(III) conjugation to organic compounds, in insect repellents and/or food additives could enhance DENV2/ZIKV loads in human cells and perhaps induce pathogenesis in infected individuals or individuals pre-exposed to such conjugated complexes. IMPORTANCE: Mosquito-borne diseases are of great concern to the mankind. Use of chemicals/repellents against mosquito bites and transmission of microbes has been the topic of interest for many years. Here, we show that thiosemicarbazone ligand(s) derived from 2-acetylethiazole or citral or 1,10-phenanthroline upon conjugation with copper(II) or cobalt(III) metal centers enhances dengue virus (serotype 2; DENV2) and/or Zika virus (ZIKV) infections in mosquito, mouse and human cells. Enhanced ZIKV/DENV2 capsid mRNA or envelope protein loads were evident in mosquito cells and human keratinocytes, when treated with compounds before/after infections. Also, treatment with copper(II) or cobalt(III) conjugated compounds increased viral titers and number of plaque formations. These studies suggest that conjugation of compounds in repellents/essential oils/natural products/food additives with copper(II) or cobalt(III) metal centers may not be safe, especially in tropical and subtropical places, where several dengue infection cases and deaths are reported annually or in places with increased ZIKV caused microcephaly.
[Mh] Termos MeSH primário: Cobalto
Complexos de Coordenação
Cobre
Vírus da Dengue/metabolismo
Queratinócitos/virologia
Carga Viral/efeitos dos fármacos
Zika virus/metabolismo
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Cobalto/química
Cobalto/farmacologia
Complexos de Coordenação/química
Complexos de Coordenação/farmacologia
Cobre/química
Cobre/farmacologia
Culicidae
Células HeLa
Seres Humanos
Queratinócitos/metabolismo
Queratinócitos/patologia
Células Vero
Proteínas do Envelope Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Viral Envelope Proteins); 3G0H8C9362 (Cobalt); 789U1901C5 (Copper)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171015
[St] Status:MEDLINE


  2 / 1168 MEDLINE  
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[PMID]:29181930
[Au] Autor:Skråning S; Lindskog BV
[Ti] Título:The Zika outbreak in Brazil: An unequal burden..
[So] Source:Tidsskr Nor Laegeforen;137(22), 2017 11 28.
[Is] ISSN:0807-7096
[Cp] País de publicação:Norway
[La] Idioma:nor
[Mh] Termos MeSH primário: Efeitos Psicossociais da Doença
Microcefalia
Infecção pelo Zika virus
[Mh] Termos MeSH secundário: Brasil/epidemiologia
Assistência à Saúde/organização & administração
Surtos de Doenças/economia
Feminino
Saúde Global
Acesso aos Serviços de Saúde
Seres Humanos
Recém-Nascido
Microcefalia/economia
Microcefalia/virologia
Mães/psicologia
Saúde Única
Pobreza
Gravidez
Complicações Infecciosas na Gravidez/economia
Complicações Infecciosas na Gravidez/epidemiologia
Complicações Infecciosas na Gravidez/virologia
Previdência Social
Saúde da Mulher
Zika virus/isolamento & purificação
Infecção pelo Zika virus/congênito
Infecção pelo Zika virus/economia
Infecção pelo Zika virus/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.4045/tidsskr.17.0655


  3 / 1168 MEDLINE  
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[PMID]:28461069
[Au] Autor:Shiryaev SA; Farhy C; Pinto A; Huang CT; Simonetti N; Elong Ngono A; Dewing A; Shresta S; Pinkerton AB; Cieplak P; Strongin AY; Terskikh AV
[Ad] Endereço:Sanford-Burnham-Prebys Medical Discovery Institute, Center for Neuroscience, Aging, and Stem Cell Research, La Jolla, CA 92037, United States.
[Ti] Título:Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists.
[So] Source:Antiviral Res;143:218-229, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The recent re-emergence of Zika virus (ZIKV) , a member of the Flaviviridae family, has become a global emergency. Currently, there are no effective methods of preventing or treating ZIKV infection, which causes severe neuroimmunopathology and is particularly harmful to the developing fetuses of infected pregnant women. However, the pathology induced by ZIKV is unique among flaviviruses, and knowledge of the biology of other family members cannot easily be extrapolated to ZIKV. Thus, structure-function studies of ZIKV proteins are urgently needed to facilitate the development of effective preventative and therapeutic agents. Like other flaviviruses, ZIKV expresses an NS2B-NS3 protease, which consists of the NS2B cofactor and the NS3 protease domain and is essential for cleavage of the ZIKV polyprotein precursor and generation of fully functional viral proteins. Here, we report the enzymatic characterization of ZIKV protease, and we identify structural scaffolds for allosteric small-molecule inhibitors of this protease. Molecular modeling of the protease-inhibitor complexes suggests that these compounds bind to the druggable cavity in the NS2B-NS3 protease interface and affect productive interactions of the protease domain with its cofactor. The most potent compound demonstrated efficient inhibition of ZIKV propagation in vitro in human fetal neural progenitor cells and in vivo in SJL mice. The inhibitory scaffolds could be further developed into valuable research reagents and, ultimately, provide a roadmap for the selection of efficient inhibitors of ZIKV infection.
[Mh] Termos MeSH primário: Sítio Alostérico
Inibidores de Proteases/química
Inibidores de Proteases/farmacologia
Proteínas não Estruturais Virais/química
Zika virus/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antivirais/antagonistas & inibidores
Antivirais/química
Sequência de Bases
Ativação Enzimática
Feminino
Flavivirus/química
Expressão Gênica
Seres Humanos
Concentração Inibidora 50
Camundongos
Modelos Moleculares
Ligação Proteica
Conformação Proteica
Domínios e Motivos de Interação entre Proteínas
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Fatores de Transcrição SOXB1/genética
Alinhamento de Sequência
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Células-Tronco
Proteínas não Estruturais Virais/efeitos dos fármacos
Proteínas Virais/química
Proteínas Virais/genética
Zika virus/química
Zika virus/genética
Zika virus/crescimento & desenvolvimento
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (NS2B protein, flavivirus); 0 (NS3 protein, flavivirus); 0 (Protease Inhibitors); 0 (SOX2 protein, human); 0 (SOXB1 Transcription Factors); 0 (Viral Nonstructural Proteins); 0 (Viral Proteins); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.13 (RNA Helicases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  4 / 1168 MEDLINE  
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[PMID]:29352307
[Au] Autor:Britch SC; Linthicum KJ; Aldridge RL; Breidenbaugh MS; Latham MD; Connelly PH; Rush MJE; Remmers JL; Kerce JD; Silcox CA; US Navy Entomology Center of Excellence Team
[Ad] Endereço:United States Department of Agriculture, Agricultural Research Service, Center for Medical, Agricultural, & Veterinary Entomology, Gainesville, Florida, United States of America.
[Ti] Título:Aerial ULV control of Aedes aegypti with naled (Dibrom) inside simulated rural village and urban cryptic habitats.
[So] Source:PLoS One;13(1):e0191555, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We conducted aerial fixed wing ultra low volume (ULV) spray trials with naled to investigate penetration of exposed and simulated cryptic habitat within opened buildings, partially sealed buildings, and outdoor locations targeting sentinel adult Aedes aegypti mosquitoes in north central Florida. Mortality was observed in open and closed buildings and outdoors, even in mosquitoes placed in cryptic habitats. Observations on the impact of building type, mosquito exposure method such as placement in cryptic habitat, and spray nozzle size on mosquito mortality are described and analyzed.
[Mh] Termos MeSH primário: Aedes
Inseticidas
Controle de Mosquitos/métodos
Naled
[Mh] Termos MeSH secundário: Aedes/virologia
Animais
Simulação por Computador
Ecossistema
Florida
Seres Humanos
Insetos Vetores/virologia
Saúde da População Rural
Saúde da População Urbana
Zika virus
Infecção pelo Zika virus/prevenção & controle
Infecção pelo Zika virus/transmissão
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Insecticides); PAM1AI9KU1 (Naled)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191555


  5 / 1168 MEDLINE  
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[PMID]:28449047
[Au] Autor:Vijaykumar S; Meurzec RW; Jayasundar K; Pagliari C; Fernandopulle Y
[Ad] Endereço:Department of Psychology, Northumbria University, UK.
[Ti] Título:What's buzzing on your feed? Health authorities' use of Facebook to combat Zika in Singapore.
[So] Source:J Am Med Inform Assoc;24(6):1155-1159, 2017 Nov 01.
[Is] ISSN:1527-974X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In 2016, Singapore grappled with one of the largest Zika outbreaks in Southeast Asia. This study examines the use of Facebook for Zika-related outreach by the Ministry of Health (MOH) and the National Environmental Agency (NEA) from March 1, 2015, to September 1, 2016, and public response to this effort. Despite nearly equivalent outreach, MOH's Facebook posts received more likes (µ = 3.49) and shares (µ = 30.11), whereas NEA's posts received more comments (µ = 4.55), with NEA posting mostly on prevention (N = 30) and MOH on situational updates (N = 24). Thematic analyses identified prevention-related posts as garnering the most likes (N = 1277), while update-related posts were most shared (N = 1059) and commented upon (N = 220). Outreach ceased briefly for 2 months after Singapore's first imported case of Zika, but increased following the outbreak of locally transmitted cases in August 2016. Public engagement was significantly higher during Zika compared with prior haze and dengue outbreaks. The results indicate the value of Facebook as a tool for rapid outreach during infectious disease outbreaks, and as a "listening" platform for those managing the situation. We discuss implications for public health communication research and policy.
[Mh] Termos MeSH primário: Surtos de Doenças/prevenção & controle
Comunicação em Saúde/métodos
Prática de Saúde Pública
Mídias Sociais
Infecção pelo Zika virus/prevenção & controle
[Mh] Termos MeSH secundário: Órgãos Governamentais
Seres Humanos
Singapura/epidemiologia
Zika virus
Infecção pelo Zika virus/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1093/jamia/ocx028


  6 / 1168 MEDLINE  
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[PMID]:29381706
[Au] Autor:Mohr EL; Block LN; Newman CM; Stewart LM; Koenig M; Semler M; Breitbach ME; Teixeira LBC; Zeng X; Weiler AM; Barry GL; Thoong TH; Wiepz GJ; Dudley DM; Simmons HA; Mejia A; Morgan TK; Salamat MS; Kohn S; Antony KM; Aliota MT; Mohns MS; Hayes JM; Schultz-Darken N; Schotzko ML; Peterson E; Capuano S; Osorio JE; O'Connor SL; Friedrich TC; O'Connor DH; Golos TG
[Ad] Endereço:Department of Pediatrics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
[Ti] Título:Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection.
[So] Source:PLoS One;13(1):e0190617, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection.
[Mh] Termos MeSH primário: Modelos Animais de Doenças
Olho/patologia
Placenta/patologia
Útero/patologia
Infecção pelo Zika virus/congênito
[Mh] Termos MeSH secundário: Animais
Feminino
Hibridização in Situ Fluorescente
Macaca mulatta
Gravidez
RNA Viral/genética
Replicação Viral
Zika virus/genética
Zika virus/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190617


  7 / 1168 MEDLINE  
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[PMID]:28469032
[Au] Autor:Chotiwan N; Brewster CD; Magalhaes T; Weger-Lucarelli J; Duggal NK; Rückert C; Nguyen C; Garcia Luna SM; Fauver JR; Andre B; Gray M; Black WC; Kading RC; Ebel GD; Kuan G; Balmaseda A; Jaenisch T; Marques ETA; Brault AC; Harris E; Foy BD; Quackenbush SL; Perera R; Rovnak J
[Ad] Endereço:Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
[Ti] Título:Rapid and specific detection of Asian- and African-lineage Zika viruses.
[So] Source:Sci Transl Med;9(388), 2017 May 03.
[Is] ISSN:1946-6242
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers.
[Mh] Termos MeSH primário: Técnicas de Amplificação de Ácido Nucleico/métodos
[Mh] Termos MeSH secundário: Animais
Culicidae
Seres Humanos
RNA Viral
Zika virus
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  8 / 1168 MEDLINE  
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[PMID]:28461071
[Au] Autor:Langsjoen RM; Auguste AJ; Rossi SL; Roundy CM; Penate HN; Kastis M; Schnizlein MK; Le KC; Haller SL; Chen R; Watowich SJ; Weaver SC
[Ad] Endereço:Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
[Ti] Título:Host oxidative folding pathways offer novel anti-chikungunya virus drug targets with broad spectrum potential.
[So] Source:Antiviral Res;143:246-251, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alphaviruses require conserved cysteine residues for proper folding and assembly of the E1 and E2 envelope glycoproteins, and likely depend on host protein disulfide isomerase-family enzymes (PDI) to aid in facilitating disulfide bond formation and isomerization in these proteins. Here, we show that in human HEK293 cells, commercially available inhibitors of PDI or modulators thereof (thioredoxin reductase, TRX-R; endoplasmic reticulum oxidoreductin-1, ERO-1) inhibit the replication of CHIKV chikungunya virus (CHIKV) in vitro in a dose-dependent manner. Further, the TRX-R inhibitor auranofin inhibited Venezuelan equine encephalitis virus and the flavivirus Zika virus replication in vitro, while PDI inhibitor 16F16 reduced replication but demonstrated notable toxicity. 16F16 significantly altered the viral genome: plaque-forming unit (PFU) ratio of CHIKV in vitro without affecting relative intracellular viral RNA quantities and inhibited CHIKV E1-induced cell-cell fusion, suggesting that PDI inhibitors alter progeny virion infectivity through altered envelope function. Auranofin also increased the extracellular genome:PFU ratio but decreased the amount of intracellular CHIKV RNA, suggesting an alternative mechanism of action. Finally, auranofin reduced footpad swelling and viremia in the C57BL/6 murine model of CHIKV infection. Our results suggest that targeting oxidative folding pathways represents a potential new anti-alphavirus therapeutic strategy.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Febre de Chikungunya/virologia
Vírus Chikungunya/efeitos dos fármacos
Vírus Chikungunya/fisiologia
Interações Hospedeiro-Patógeno/fisiologia
[Mh] Termos MeSH secundário: Infecções por Alphavirus/virologia
Animais
Auranofina/antagonistas & inibidores
Febre de Chikungunya/mortalidade
Vírus Chikungunya/patogenicidade
Modelos Animais de Doenças
Vírus da Encefalite Equina Venezuelana/efeitos dos fármacos
Flavivirus/efeitos dos fármacos
Células HEK293
Seres Humanos
Glicoproteínas de Membrana
Camundongos
Camundongos Endogâmicos C57BL
Isomerases de Dissulfetos de Proteínas/farmacologia
Dobramento de Proteína
Tiorredoxina Dissulfeto Redutase/farmacologia
Proteínas do Envelope Viral/metabolismo
Replicação Viral/efeitos dos fármacos
Zika virus/efeitos dos fármacos
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Membrane Glycoproteins); 0 (Viral Envelope Proteins); 3H04W2810V (Auranofin); EC 1.8.1.9 (Thioredoxin-Disulfide Reductase); EC 5.3.4.1 (Protein Disulfide-Isomerases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  9 / 1168 MEDLINE  
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[PMID]:28461070
[Au] Autor:Albulescu IC; Kovacikova K; Tas A; Snijder EJ; van Hemert MJ
[Ad] Endereço:Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
[Ti] Título:Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles.
[So] Source:Antiviral Res;143:230-236, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is a mosquito-borne flavivirus that mostly causes asymptomatic infections or mild disease characterized by low-grade fever, rash, conjunctivitis, and malaise. However, the recent massive ZIKV epidemics in the Americas have also linked ZIKV infection to fetal malformations like microcephaly and Guillain-Barré syndrome in adults, and have uncovered previously unrecognized routes of vertical and sexual transmission. Here we describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug, which was more recently shown to inhibit multiple viruses. In cell culture-based assays, using reduction of cytopathic effect as read-out, suramin had an EC of ∼40 µM and a selectivity index of 48. In single replication cycle experiments, suramin treatment also caused a strong dose-dependent decrease in intracellular ZIKV RNA levels and a >3-log reduction in infectious progeny titers. Time-of-addition experiments revealed that suramin inhibits a very early step of the replication cycle as well as the release of infectious progeny. Only during the first 2 h of infection suramin treatment strongly reduced the fraction of cells that became infected with ZIKV, suggesting the drug affects virus binding/entry. Binding experiments at 4 °C using S-labeled ZIKV demonstrated that suramin interferes with attachment to host cells. When suramin treatment was initiated post-entry, viral RNA synthesis was unaffected, while both the release of genomes and the infectivity of ZIKV were reduced. This suggests the compound also affects virion biogenesis, possibly by interfering with glycosylation and the maturation of ZIKV during its traffic through the secretory pathway. The inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broad-spectrum activity warrant further evaluation of this compound as a potential therapeutic.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Vírion/efeitos dos fármacos
Ligação Viral/efeitos dos fármacos
Liberação de Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Efeito Citopatogênico Viral/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Flavivirus/efeitos dos fármacos
Glicosilação/efeitos dos fármacos
Ácido Micofenólico/administração & dosagem
Ácido Micofenólico/antagonistas & inibidores
RNA Viral/análise
RNA Viral/biossíntese
RNA Viral/efeitos dos fármacos
Suramina/administração & dosagem
Fatores de Tempo
Células Vero
Internalização do Vírus/efeitos dos fármacos
Zika virus/crescimento & desenvolvimento
Zika virus/fisiologia
Infecção pelo Zika virus/tratamento farmacológico
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Viral); 6032D45BEM (Suramin); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28457855
[Au] Autor:Tan CW; Sam IC; Chong WL; Lee VS; Chan YF
[Ad] Endereço:Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: tancw86@gmail.com.
[Ti] Título:Polysulfonate suramin inhibits Zika virus infection.
[So] Source:Antiviral Res;143:186-194, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log PFU viral reduction with IC value of ∼2.5-5 µg/ml (1.93 µM-3.85 µM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Infecção pelo Zika virus/prevenção & controle
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais
Cercopithecus aethiops
Cloratos/farmacologia
DNA Helicases/metabolismo
Sulfato de Dextrana/antagonistas & inibidores
Flavivirus/efeitos dos fármacos
Glicosaminoglicanos/farmacologia
Heparina/análogos & derivados
Heparina/química
Heparina/farmacologia
Heparitina Sulfato/farmacologia
Concentração Inibidora 50
Camundongos
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
RNA Helicases/química
RNA Helicases/efeitos dos fármacos
Serina Endopeptidases/química
Serina Endopeptidases/efeitos dos fármacos
Suramina/administração & dosagem
Células Vero
Proteínas do Envelope Viral/metabolismo
Proteínas não Estruturais Virais/química
Proteínas não Estruturais Virais/efeitos dos fármacos
Internalização do Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/fisiologia
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Chlorates); 0 (Glycosaminoglycans); 0 (NS3 protein, flavivirus); 0 (Viral Envelope Proteins); 0 (Viral Nonstructural Proteins); 6032D45BEM (Suramin); 9005-49-6 (Heparin); 9042-14-2 (Dextran Sulfate); 9050-30-0 (Heparitin Sulfate); EC 3.4.21.- (Serine Endopeptidases); EC 3.6.4.- (DNA Helicases); EC 3.6.4.13 (RNA Helicases); T95DR77GMR (sodium chlorate)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE



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