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https://www.readbyqxmd.com/read/28324644/synthesis-of-the-t-705-ribonucleoside-and-ribonucleotide-and-studies-on-the-chemical-stability
#1
Johanna Huchting, Matthias Winkler, Hiba Nasser, Chris Meier
T-705 (favipiravir) is a fluorinated hydroxypyrazine carboxamide that exhibits antiviral activities against a variety of RNA viruses. Due to the lack of potent agents to combat these infections caused by a large number of these high-impacting pathogens, huge emphasis has been put on the studies of T-705's antiviral properties and its mechanism of action. T-705 acts as a nucleobase analogue; hence, it is metabolized to the corresponding ribonucleoside triphosphate intracellularly. We herein report a reliable synthesis of T-705-ribonucleoside and its 5'-monophosphate...
March 21, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28324594/polymers-in-the-delivery-of-sirna-for-the-treatment-of-virus-infections
#2
REVIEW
Nicholas Reynolds, Megan Dearnley, Tracey M Hinton
Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a "magic bullet", due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28323869/tyrosine-mutated-aav2-mediated-shrna-silencing-of-pten-promotes-axon-regeneration-of-adult-optic-nerve
#3
ZhengRu Huang, ZiZhong Hu, Ping Xie, QingHuai Liu
Activating PI3K/AKT/mTOR signaling pathway via deleting phosphatase and tensin homolog (PTEN) has been confirmed to enhance intrinsic growth capacity of neurons to facilitate the axons regeneration of central nervous system after injury. Considering conditional gene deletion is currently not available in clinical practice, we exploited capsid residue tyrosine 444 to phenylalanine mutated single-stranded adeno-associated virus serotype 2 (AAV2) as a vector delivering short hairpin RNA to silence PTEN to promote retinal ganglion cells (RGCs) survival and axons regeneration in adult rat optic nerve axotomy paradigm...
2017: PloS One
https://www.readbyqxmd.com/read/28323565/surveillance-for-highly-pathogenic-avian-influenza-in-wild-turkeys-meleagris-gallopavo-of-minnesota-during-2015-outbreaks-in-domestic-poultry
#4
Christopher S Jennelle, Michelle Carstensen, Erik C Hildebrand, Paul C Wolf, Daniel A Grear, Hon S Ip, Louis Cornicelli
An outbreak of a novel reassortant of highly pathogenic avian influenza A (H5N2) virus (HPAIV) decimated domestic turkeys ( Meleagris gallopavo ) from March through mid-June, 2015 in the state of Minnesota, USA. In response, as part of broader surveillance efforts in wild birds, we designed a pilot effort to sample and test hunter-harvested Wild Turkeys ( Meleagris gallopavo ) for HPAIV in Minnesota counties with known infected poultry facilities. We also collected opportunistic samples from dead Wild Turkeys or live Wild Turkeys showing neurologic signs (morbidity and mortality samples) reported by the public or state agency personnel...
March 21, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28323529/altered-expression-of-a-chloroplast-protein-affects-the-outcome-of-virus-and-nematode-infection
#5
Elena Ganusova, J Hollis Rice, Timothy Scott Carlew, Akshita Patel, Emmanuel Perrodin-Njoku, Tarek Hewezi, Tessa M Burch-Smith
The chloroplast-resident RNA helicase ISE2 (INCREASED SIZE EXCLUSION LIMIT 2) can modulate the formation and distribution of plasmodesmata and intercellular trafficking. We have determined that ISE2 expression is induced by viral infection. Therefore the responses of Nicotiana benthamiana plants with varying levels of ISE2 expression to infection by Tobacco mosaic virus (TMV) and Turnip mosaic virus (TuMV) were examined. Surprisingly, increased or decreased ISE2 expression led to faster viral systemic spread and is some cases enhanced systemic necrosis...
March 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28323402/single-particle-observation-of-sv40-vp1-polyanion-induced-assembly-shows-that-substrate-size-and-structure-modulate-capsid-geometry
#6
Chenglei Li, Andrew R Kneller, Stephen C Jacobson, Adam Zlotnick
Simian virus 40 capsid protein (VP1) is a unique system for studying substrate-dependent assembly of a nanoparticle. Here, we investigate a simplest case of this system where twelve VP1 pentamers and a single polyanion, e.g. RNA, form a T=1 particle. To test the roles of polyanion substrate length and structure during assembly, we characterized the assembly products with size exclusion chromatography, transmission electron microscopy, and single-particle resistive-pulse sensing. We found that a 500 nt RNA has the optimal length and structure for assembly of uniform T=1 particles...
March 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28320169/probable-zika-virus-associated-guillain-barr%C3%A3-syndrome-challenges-with-clinico-laboratory-diagnosis
#7
Eliza Miller, Zoe Becker, Daniel Shalev, Christopher T Lee, Comana Cioroiu, Kiran Thakur
A 55year old woman in New York City presented in May 2016 with progressive weakness, ataxia, paresthesia, and areflexia, shortly after returning from the Dominican Republic. Lumbar puncture revealed cytoalbuminological dissociation. Due to her recent travel, Zika-associated Guillain Barré syndrome (GBS) was suspected and she underwent evaluation for recent flavivirus exposure. Zika virus RNA was not detected in serum, but Zika virus immunoglobulin M (IgM) was detected in both serum and cerebrospinal fluid...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319790/within-host-rna-virus-persistence-mechanisms-and-consequences
#8
REVIEW
Richard E Randall, Diane E Griffin
In a prototypical response to an acute viral infection it would be expected that the adaptive immune response would eliminate all virally infected cells within a few weeks of infection. However many (non-retrovirus) RNA viruses can establish 'within host' persistent infections that occasionally lead to chronic or reactivated disease. Despite the importance of 'within host' persistent RNA virus infections, much has still to be learnt about the molecular mechanisms by which RNA viruses establish persistent infections, why innate and adaptive immune responses fail to rapidly clear these infections, and the epidemiological and potential disease consequences of such infections...
March 17, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28318141/zika-virus-induced-cellular-remodeling
#9
Evan D Rossignol, Kristen N Peters, John H Connor, Esther Bullitt
Zika virus (ZIKV) has been associated with morbidities such as Guillain-Barré, infant microcephaly, and ocular disease. The spread of this positive-sense, single-stranded RNA virus and its growing public health threat underscore gaps in our understanding of basic ZIKV virology. To advance knowledge of the virus replication cycle within mammalian cells, we use serial section three-dimensional electron tomography to demonstrate the widespread remodeling of intracellular membranes upon infection with ZIKV. We report extensive structural rearrangements of the endoplasmic reticulum and reveal stages of the ZIKV viral replication cycle...
March 20, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28316131/evaluation-of-potential-rna-interference-target-genes-to-control-cotton-mealybug-phenacoccus-solenopsis-hemiptera-pseudococcuidae
#10
Arif M Khan, Muhammad Ashfaq, Azhar A Khan, Muhammad T Naseem, Shahid Mansoor
RNA interference (RNAi) of vital insect genes is a potential tool for targeted pest control. However, selection of the right target genes is a challenge because the RNAi efficacy is known to vary among insect species. Cotton mealybug, Phenacoccus solenopsis, is a phloem-feeding economically important crop pest. We evaluated the RNAi of two vital genes, Bursicon (PsBur) and V-ATPase (PsV-ATPase) as potential targets in P. solenopsis for its control. PCR fragments of PsBur and PsV-ATPase were amplified using cDNA synthesized from the total RNA...
March 18, 2017: Insect Science
https://www.readbyqxmd.com/read/28316018/a-novel-vitivirus-like-sequence-found-in-arracacia-xanthorrhiza-plants-by-high-throughput-sequencing
#11
Layssa M Oliveira, Anelise F Orílio, Alice K Inoue-Nagata, Tatsuya Nagata, Rosana Blawid
High throughput sequencing (HTS) is a very powerful tool for detecting and discovering novel viral-like sequences without prior knowledge of the sequence. Here we describe the complete genome of a new vitivirus-like sequence that was found in arracacha (Arracacia xanthorrhiza) plants using HTS technology. The complete genome sequence was validated by Sanger sequencing. The genomic organization of the new putative vitivirus resembles that of grapevine virus B (GVB) and grapevine virus D (GVD). The putative coat protein showed 41 to 49% identity with similar proteins of known vitiviruses, while the RNA-dependent RNA polymerase shared 52 to 55% identity with those encoded by grapevine vitiviruses...
March 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28316014/rescue-of-recombinant-newcastle-disease-virus-a-short-history-of-how-it-all-started
#12
REVIEW
Aidin Molouki, Ben Peeters
Reverse genetics of viruses has come a long way, and many recombinant viruses have been generated since the first successful "rescues" were reported in the late 1970s. Recombinant Newcastle disease virus (rNDV), a non-segmented negative-sense RNA virus (NSNSV), was first rescued in 1999 using a reverse genetics approach similar to that reported for other recombinant viruses of the order Mononegavirales a few years before. The route from an original NDV isolate to the generation of its recombinant counterpart requires many steps that have to be sequentially and carefully completed...
March 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28315707/combined-administration-of-synthetic-rna-and-a-conventional-vaccine-improves-immune-responses-and-protection-against-foot-and-mouth-disease-virus-in-swine
#13
Belén Borrego, Esther Blanco, Miguel Rodríguez Pulido, Francisco Mateos, Gema Lorenzo, Sabrina Cardillo, Eliana Smitsaart, Francisco Sobrino, Margarita Sáiz
Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs...
March 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28315476/comparative-analysis-of-protein-evolution-in-the-genome-of-pre-epidemic-and-epidemic-zika-virus
#14
Arunachalam Ramaiah, Lei Dai, Deisy Contreras, Sanjeev Sinha, Ren Sun, Vaithilingaraja Arumugaswami
Zika virus (ZIKV) causes microcephaly in congenital infection, neurological disorders, and poor pregnancy outcome and no vaccine is available for use in humans or approved. Although ZIKV was first discovered in 1947, the exact mechanism of virus replication and pathogenesis remains unknown. Recent outbreaks of Zika virus in the Americas clearly suggest a human-mosquito cycle or urban cycle of transmission. Understanding the conserved and adaptive features in the evolution of ZIKV genome will provide a hint on the mechanism of ZIKV adaptation to a new cycle of transmission...
March 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28315051/development-of-antibody-modified-chitosan-nanoparticles-for-the-targeted-delivery-of-sirna-across-the-blood-brain-barrier-as-a-strategy-for-inhibiting-hiv-replication-in-astrocytes
#15
Jijin Gu, Karam Al-Bayati, Emmanuel A Ho
RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands...
March 17, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#16
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 8, 2017: Immunity
https://www.readbyqxmd.com/read/28304114/antiviral-and-cytostatic-evaluation-of-5-1-halo-2-sulfonylvinyl-and-5-2-furyl-uracil-nucleosides
#17
Zhiwei Wen, Sazzad H Suzol, Jufang Peng, Yong Liang, Robert Snoeck, Graciela Andrei, Sandra Liekens, Stanislaw F Wnuk
Transition metal-catalyzed halosulfonylation of 5-ethynyl uracil nucleosides provided (E)-5-(1-chloro-2-tosylvinyl)uridines. Tetrabutylammonium fluoride-mediated direct CH arylation of 5-iodouracil nucleosides with furan or 2-heptylfuran gave 5-furyl-substituted nucleosides without the necessity of using the organometallic substrates. These two classes of 5-substituted uracil nucleosides as well their corresponding ester derivatives were tested against a broad range of DNA and RNA viruses and the human immunodeficiency virus (HIV)...
March 17, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28303593/sb-9200-a-novel-agonist-of-innate-immunity-shows-potent-antiviral-activity-against-resistant-hcv-variants
#18
Meleri Jones, Morven E Cunningham, Peter Wing, Sampath DeSilva, Rupa Challa, Anjaneyulu Sheri, Seetharamaiyer Padmanabhan, Radhakrishnan P Iyer, Brent E Korba, Nezam Afdhal, Graham R Foster
SB 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the RIG-I and NOD2 pathways. SB 9200 has broad-spectrum antiviral activity against RNA viruses including hepatitis C virus (HCV), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis B virus (HBV) in vitro and in vivo. In phase I clinical trials in chronically infected HCV patients, SB 9200 has been shown to reduce HCV RNA by up to 1.9 log10 . Here, we demonstrate the antiviral activity of SB 9200 against a HCV replicon system and patient derived virus...
March 17, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28302581/targeting-ets1-with-rnai-based-supramolecular-nanoassemblies-for-multidrug-resistant-breast-cancer-therapy
#19
Min Wu, Xingang Liu, Weihong Jin, Yongbing Li, Yang Li, Qinglian Hu, Paul K Chu, Guping Tang, Yuan Ping
Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically...
March 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28302528/association-between-enteric-protozoan-parasites-and-gastrointestinal-illness-among-hiv-and-tuberculosis-infected-individuals-in-the-chowke-district-southern-mozambique
#20
María José Irisarri-Gutiérrez, Marta Hernández-de Mingo, Aida de Lucio, Horacio Gil, Lucía Morales, Raimundo Seguí, Edy Nacarapa, Carla Muñoz-Antolí, Fernando Jorge Bornay-Llinares, José Guillermo Esteban, David Carmena
Human immune deficiency virus (HIV) and tuberculosis (TB) infections remain major public health issues globally, particularly in sub-Saharan Africa. Impairment of both cell-mediated and humoral immunity by HIV and/or TB infections may limit the host's defences against other pathogens, including the diarrheagenic protozoan Cryptosporidium spp., Giardia intestinalis, and Entamoeba histolytica. During September-December 2015 a cross-sectional study was conducted to assess the prevalence and molecular diversity of these enteric parasites among HIV- and/or TB-infected patients at a medical reference centre in Chowke district, southern Mozambique...
March 14, 2017: Acta Tropica
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