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https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#1
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087772/possible-roles-of-new-mutations-shared-by-asian-and-american-zika-viruses
#2
Shozo Yokoyama, William T Starmer
Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 x 10(-3)/nucleotide site/year and subsequently increased significantly in most of its descendants...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27993855/obatoclax-inhibits-alphavirus-membrane-fusion-by-neutralizing-the-acidic-environment-of-endocytic-compartments
#3
Finny S Varghese, Kai Rausalu, Marika Hakanen, Sirle Saul, Beate M Kümmerer, Petri Susi, Andres Merits, Tero Ahola
As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses including chikungunya virus, West Nile virus, influenza virus etc. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins was previously determined to be antiviral against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses like chikungunya virus (EC50 = 0...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27934765/zika-virus-produces-noncoding-rnas-using-a-multi-pseudoknot-structure-that-confounds-a-cellular-exonuclease
#4
Benjamin M Akiyama, Hannah M Laurence, Aaron R Massey, David A Costantino, Xuping Xie, Yujiao Yang, Pei-Yong Shi, Jay C Nix, J David Beckham, Jeffrey S Kieft
The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses...
December 2, 2016: Science
https://www.readbyqxmd.com/read/27930336/resistance-mutation-conserved-between-insects-and-mites-unravels-the-benzoylurea-insecticide-mode-of-action-on-chitin-biosynthesis
#5
Vassilis Douris, Denise Steinbach, Rafaela Panteleri, Ioannis Livadaras, John Anthony Pickett, Thomas Van Leeuwen, Ralf Nauen, John Vontas
Despite the major role of chitin biosynthesis inhibitors such as benzoylureas (BPUs) in the control of pests in agricultural and public health for almost four decades, their molecular mode of action (MoA) has in most cases remained elusive. BPUs interfere with chitin biosynthesis and were thought to interact with sulfonylurea receptors that mediate chitin vesicle transport. Here, we uncover a mutation (I1042M) in the chitin synthase 1 (CHS1) gene of BPU-resistant Plutella xylostella at the same position as the I1017F mutation reported in spider mites that confers etoxazole resistance...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27893824/analysis-of-synonymous-codon-usage-bias-of-zika-virus-and-its-adaption-to-the-hosts
#6
Hongju Wang, Siqing Liu, Bo Zhang, Wenqiang Wei
Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators...
2016: PloS One
https://www.readbyqxmd.com/read/27886338/frequency-of-the-val1016ile-mutation-on-the-kdr-gene-in-aedes-aegypti-diptera-culicidae-in-south-brazil
#7
M L Collet, C Frizzo, E Orlandin, L D P Rona, J C Nascimento, M A E Montano, G A Müller, G Wagner
Recently, the number of Aedes aegypti foci has increased in west of Santa Catarina, south Brazil, which has increased concern regarding mosquito-borne disease outbreaks such as dengue fever, Zika virus, and chikungunya. Therefore, it is important to monitor genetic resistance to insecticides through "knockdown resistance". Homozygosity (Ile/Ile) at position 1016 in the coding region of a voltage-dependent sodium channel gene (Nav) may induce resistance to pyrethroid insecticides. We evaluated the frequency of these alleles in A...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27881148/susceptibility-profile-and-metabolic-mechanisms-involved-in-aedes-aegypti-and-aedes-albopictus-resistant-to-ddt-and-deltamethrin-in-the-central-african-republic
#8
Carine Ngoagouni, Basile Kamgang, Cécile Brengues, Gildas Yahouedo, Christophe Paupy, Emmanuel Nakouné, Mirdad Kazanji, Fabrice Chandre
BACKGROUND: Aedes aegypti and Ae. albopictus are the main epidemic vectors of dengue, chikungunya and Zika viruses worldwide. Their control during epidemics relies mainly on control of larvae and adults with insecticides. Unfortunately, loss of susceptibility of both species to several insecticide classes limits the efficacy of interventions. In Africa, where Aedes-borne viruses are of growing concern, few data are available on resistance to insecticides. To fill this gap, we assessed the susceptibility to insecticides of Ae...
November 24, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27870689/zika-virus-and-diagnostics
#9
Claudia Raja Gabaglia
PURPOSE OF REVIEW: The purpose of this review is to present what is known about the Zika virus (ZIKV) at the time of writing this review. The viral structure and its phylogeny, as well as the limitations of current available techniques used for diagnosis, are discussed. RECENT FINDINGS: Crystallography and cryo-electron microscopy of the whole ZIKV, or a few of its proteins, are confirming its overall antigenic relatedness to other flaviviruses. Sequencing has revealed its dynamic genetic variation and has placed the Western cluster of Zika isolates within the Asian phylogenic tree...
November 18, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27869391/-first-report-of-the-f1534c-mutation-associated-with-cross-resistance-to-ddt-and-pyrethroids-in-aedes-aegypti-from-colombia
#10
María Claudia Atencia, María De Jesús Pérez, María Cristina Jaramillo, Sandy Milena Caldera, Suljey Cochero, Eduar Elías Bejarano
The main strategy for the control of Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is based on the use of insecticides to reduce its populations. However, their use has led to insect resistance to these chemicals. Objective: To determine the presence of the F1534C mutation associated with cross-resistance to DDT and pyrethroids in A. aegypti in Sincelejo, Colombia. Materials and methods: We studied nine specimens of A. aegypti that showed resistance to lambdacyhalothrin in bioassays developed by the Secretaría de Salud de Sucre...
September 1, 2016: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/27809228/sodium-channel-mutations-and-pyrethroid-resistance-in-aedes-aegypti
#11
REVIEW
Yuzhe Du, Yoshiko Nomura, Boris S Zhorov, Ke Dong
Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr), in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes...
October 31, 2016: Insects
https://www.readbyqxmd.com/read/27805221/analysis-of-worldwide-sequence-mutations-in-zika-virus-proteins-e-ns1-ns3-and-ns5-from-a-structural-point-of-view
#12
C F Baez, V A Barel, A M T de Souza, C R Rodrigues, R B Varella, N Cirauqui
Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27787521/zika-virus-elicits-p53-activation-and-genotoxic-stress-in-human-neural-progenitors-similar-to-mutations-involved-in-severe-forms-of-genetic-microcephaly-and-p53
#13
Vincent El Ghouzzi, Federico T Bianchi, Ivan Molineris, Bryan C Mounce, Gaia E Berto, Malgorzata Rak, Sophie Lebon, Laetitia Aubry, Chiara Tocco, Marta Gai, Alessandra Ma Chiotto, Francesco Sgrò, Gianmarco Pallavicini, Etienne Simon-Loriere, Sandrine Passemard, Marco Vignuzzi, Pierre Gressens, Ferdinando Di Cunto
Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV and microcephaly. ZIKV infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. However, the mechanisms leading to these phenotypes are still largely obscure. In this report, we explored the possible similarities between transcriptional responses induced by ZIKV in human neural progenitors and those elicited by three different genetic mutations leading to severe forms of microcephaly in mice...
October 27, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27742355/pyrethroid-resistance-in-aedes-aegypti-and-aedes-albopictus-important-mosquito-vectors-of-human-diseases
#14
REVIEW
Letícia B Smith, Shinji Kasai, Jeffrey G Scott
Aedes aegypti and A. albopictus mosquitoes are vectors of important human disease viruses, including dengue, yellow fever, chikungunya and Zika. Pyrethroid insecticides are widely used to control adult Aedes mosquitoes, especially during disease outbreaks. Herein, we review the status of pyrethroid resistance in A. aegypti and A. albopictus, mechanisms of resistance, fitness costs associated with resistance alleles and provide suggestions for future research. The widespread use of pyrethroids has given rise to many populations with varying levels of resistance worldwide, albeit with substantial geographical variation...
October 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27729643/evolution-of-codon-usage-in-zika-virus-genomes-is-host-and-vector-specific
#15
Azeem Mehmood Butt, Izza Nasrullah, Raheel Qamar, Yigang Tong
The codon usage patterns of viruses reflect the evolutionary changes that allow them to optimize their survival and adapt their fitness to the external environment and, most importantly, their hosts. Here we report the genotype-specific codon usage patterns of Zika virus (ZIKV) strains from the current and previous outbreaks. Several genotype-specific and common codon usage traits were noted in the ZIKV coding sequences, indicating their independent evolutionary origins from a common ancestor. The overall influence of natural selection was more profound than that of mutation pressure, acting on a specific set of viral genes in the Asian-genotype ZIKV strains from the recent outbreak...
October 12, 2016: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/27729507/how-did-zika-virus-emerge-in-the-pacific-islands-and-latin-america
#16
John H-O Pettersson, Vegard Eldholm, Stephen J Seligman, Åke Lundkvist, Andrew K Falconar, Michael W Gaunt, Didier Musso, Antoine Nougairède, Remi Charrel, Ernest A Gould, Xavier de Lamballerie
The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV...
October 11, 2016: MBio
https://www.readbyqxmd.com/read/27670692/phylogenesys-and-homology-modeling-in-zika-virus-epidemic-food-for-thought
#17
Silvia Angeletti, Alessandra Lo Presti, Marta Giovanetti, Alba Grifoni, Massimo Amicosante, Marco Ciotti, Luiz-Carlos J Alcantara, Eleonora Cella, Massimo Ciccozzi
Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified...
October 2016: Pathogens and Global Health
https://www.readbyqxmd.com/read/27658737/zika-virus-replicons-for-drug-discovery
#18
Xuping Xie, Jing Zou, Chao Shan, Yujiao Yang, Dieudonné Buh Kum, Kai Dallmeier, Johan Neyts, Pei-Yong Shi
The current epidemic of Zika virus (ZIKV) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. Here we report two ZIKV replicon systems: a luciferase replicon that can differentiate between viral translation and RNA synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. The transient replicon was used to evaluate the effect of an NS5 polymerase mutation on viral RNA synthesis and to analyze a known ZIKV inhibitor...
October 2016: EBioMedicine
https://www.readbyqxmd.com/read/27647195/available-evidence-of-association-between-zika-virus-and-microcephaly
#19
REVIEW
Jing Wu, Da-Yong Huang, Jun-Tao Ma, Ying-Hua Ma, Yi-Fei Hu
OBJECTIVE: To clarify the possible association between the Zika virus (ZIKV) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly. DATA SOURCES: We did a comprehensive literature review with the keywords "zika" and/or "microcephaly" from inception to May 27, 2016, with PubMed. STUDY SELECTION: Studies were included and analyzed if they met all of the following criteria: "probable or confirmed infant microcephaly" and "probable or confirmed ZIKV infection among mothers or infants"...
2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27617437/tissues-derived-from-reprogrammed-wharton-s-jelly-stem-cells-of-the-umbilical-cord-provide-an-ideal-platform-to-study-the-effects-of-glucose-zika-virus-and-other-agents-on-the-fetus
#20
Chui-Yee Fong, Arijit Biswas, Walter Stunkel, Yap-Seng Chong, Ariff Bongso
The infants of mothers with gestational diabetes mellitus (GDM) have an increased risk of metabolic and cardiovascular disease. It has been difficult to study the direct effects of maternal hyperglycemia on the fetus because of inaccessibility of fetal tissues. The development of tissues that simulate the function of fetal organs using stem cell technology provides an unprecedented opportunity to study this disorder. Stem cells in the Wharton's jelly of the umbilical cord (hWJSCs), possess unique properties that are different from other stem cells...
September 12, 2016: Journal of Cellular Biochemistry
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