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Antiviral Research

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https://www.readbyqxmd.com/read/29432776/establishment-of-cre-mediated-hbv-recombinant-cccdna-rcccdna-cell-line-for-cccdna-biology-and-antiviral-screening-assays
#1
Min Wu, Jin Li, Lei Yue, Lu Bai, Yaming Li, Jieliang Chen, Xiaonan Zhang, Zhenghong Yuan
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), existing in hepatocyte nuclei as a stable minichromosome, plays a central role in the life cycle of the virus and permits the persistence of infection. Despite being essential for HBV infection, little is known about the molecular mechanisms of cccDNA formation, regulation and degradation, and there is no therapeutic agents directly targeting cccDNA, fore mostly due to the lack of robust, reliable and quantifiable HBV cccDNA models. In this study, combined the Cre/loxP and sleeping beauty transposons system, we established HepG2-derived cell lines integrated with 2-60 copies of monomeric HBV genome flanked by loxP sites (HepG2-HBV/loxP)...
February 9, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29428508/the-molecular-tweezer-clr01-inhibits-ebola-and-zika-virus-infection
#2
Annika E Röcker, Janis A Müller, Erik Dietzel, Mirja Harms, Franziska Krüger, Christian Heid, Andrea Sowislok, Camilla Frich Riber, Alexandra Kupke, Sina Lippold, Jens von Einem, Judith Beer, Bernd Knöll, Stephan Becker, Jonas Schmidt-Chanasit, Markus Otto, Olli Vapalahti, Alexander N Zelikin, Gal Bitan, Thomas Schrader, Jan Münch
Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule previously has been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner...
February 8, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29427676/in-vitro-susceptibility-to-st-246-and-cidofovir-corroborates-the-phylogenetic-separation-of-brazilian-vaccinia-virus-into-two-clades
#3
Mariana A Pires, Nathália F S Rodrigues, Danilo B de Oliveira, Felipe L de Assis, Galileu B Costa, Erna G Kroon, Bruno E F Mota
The Orthopoxvirus (OPV) genus of the Poxviridae family contains several human pathogens, including Vaccinia virus (VACV), which have been implicating in outbreaks of a zoonotic disease called Bovine Vaccinia in Brazil. So far, no approved treatment exists for OPV infections, but ST-246 and Cidofovir (CDV) are now in clinical development. Therefore, the objective of this work was to evaluate the susceptibility of five strains of Brazilian VACV (Br-VACV) to ST-246 and Cidofovir. The susceptibility of these strains to both drugs was evaluated by plaque reduction assay, extracellular virus's quantification in the presence of ST-246 and one-step growth curve in cells treated with CDV...
February 7, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29427675/relevance-of-non-synonymous-thymidine-kinase-mutations-for-antiviral-resistance-of-recombinant-herpes-simplex-virus-type-2-strains
#4
Anne-Kathrin Brunnemann, Anja Hoffmann, Stefanie Deinhardt-Emmer, Claus-Henning Nagel, Ruben Rose, Helmut Fickenscher, Andreas Sauerbrei, Andi Krumbholz
Therapy or prophylaxis of herpes simplex virus type 2 (HSV-2) infections with the nucleoside analog aciclovir (ACV) can lead to the emergence of drug-resistant HSV-2 strains, particularly in immunocompromised patients. In this context, multiple amino acid (aa) changes can accumulate in the ACV-converting viral thymidine kinase (TK) which hampers sequence-based diagnostics significantly. In this study, the so far unknown or still doubted relevance of several individual aa changes for drug resistance in HSV-2 was clarified...
February 7, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29427674/phage-display-antibodies-against-ectromelia-virus-that-neutralize-variola-virus-selection-and-implementation-for-p35-neutralizing-epitope-mapping
#5
Yana Khlusevich, Andrey Matveev, Ivan Baykov, Leonid Bulychev, Nikolai Bormotov, Ivan Ilyichev, Georgiy Shevelev, Vera Morozova, Dmitrii Pyshnyi, Nina Tikunova
In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV...
February 7, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29425831/gs-9620-inhibits-enterovirus-71-replication-mainly-through-the-nf-%C3%AE%C2%BAb-and-pi3k-akt-signaling-pathways
#6
Qian Zhang, Binbin Zhao, Xin Chen, Nan Song, Jing Wu, Guangchao Li, Pin Yu, Yunlin Han, Jiangning Liu, Chuan Qin
Human enterovirus 71 (EV71) is the second most common cause of hand, foot, and mouth disease (HFMD), which can occur as a severe epidemic especially among children under 5-years old. New and improved treatment strategies to control EV71 infection are therefore urgently required. The heterocyclic compound GS-9620, a potent and selective agonist of Toll-like receptor 7 (TLR7), has been reported to activate plasmacytoid dendritic cells (pDCs), and suppress HBV as well as HIV replication. In this study, we indicated that GS-9620 also could inhibit EV71 replication in the mouse model of EV71 infection...
February 6, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29425830/metal-chelating-3-hydroxypyrimidine-2-4-diones-inhibit-human-cytomegalovirus-pul89-endonuclease-activity-and-virus-replication
#7
Yan Wang, Jing Tang, Zhengqiang Wang, Robert J Geraghty
Human cytomegalovirus terminase complex cleaves the concatemeric genomic viral DNA into unit lengths during genome packaging and particle assembly. Terminase complex ATPase and endonuclease activity is provided by the viral protein pUL89. pUL89 is an attractive drug target because its activities are required for infectious virus production. A domain located in the C-terminus of pUL89 has an RNase H/integrase-like fold and endonuclease activity that can be inhibited by compounds featuring a chelating triad motif...
February 6, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29421321/2017-international-meeting-of-the-global-virus-network
#8
REVIEW
Mike Catton, Glenda Gray, Diane Griffin, Hideki Hasegawa, Stephen Kent, Jason Mackenzie, Edward McSweegan, Natalia Mercer, Linfa Wang
The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 40 GVN Centers of Excellence and 6 Affiliate laboratories in 24 countries. The 2017 meeting was held from September 25-27 in Melbourne, Australia, and was hosted by the Peter Doherty Institute for Infection and Immunity and the Institut Pasteur. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including the recent Zika epidemic, infections by human papillomavirus, influenza, HIV, hepatitis C, HTLV-1, and chikungunya viruses, and new and emerging viruses in the Australasia region...
February 5, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29421320/retinoic-acid-receptor-%C3%AE-a-potential-therapeutic-target-in-the-inhibition-of-adenovirus-replication
#9
Xiaolong Wang, Qiling Zhang, Zhe Zhou, Manjiao Liu, Yubao Chen, Jianbo Li, Linlin Xu, Jing Guo, Qingjun Li, Jing Yang, Shengqi Wang
Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus-host interactions, and several key host molecules involved in the HAdV infection process were identified...
February 5, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29407486/antiviral-and-anti-inflammatory-activity-of-budesonide-against-human-rhinovirus-infection-mediated-via-autophagy-activation
#10
Seong-Ryeol Kim, Jae-Hyoung Song, Jae-Hee Ahn, Geun-Shik Lee, Huijeong Ahn, Sung-Il Yoon, Seung Goo Kang, Pyeung-Hyeun Kim, Sang-Min Jeon, Eun-Ji Choi, Sooyoung Shin, Younggil Cha, Sungchan Cho, Dong-Eun Kim, Sun-Young Chang, Hyun-Jeong Ko
Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor...
February 1, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29410019/novel-secondary-mutations-c56s-and-g149a-confer-resistance-to-hiv-1-integrase-strand-transfer-inhibitors
#11
Tomokazu Yoshinaga, Takahiro Seki, Shigeru Miki, Tadashi Miyamoto, Akemi Suyama-Kagitani, Shinobu Kawauchi-Miki, Masanori Kobayashi, Akihiko Sato, Eugene Stewart, Mark Underwood, Tamio Fujiwara
Cabotegravir (CAB, S/GSK1265744) is an investigational second-generation integrase strand transfer inhibitor (INSTI) with a chemical structure similar to dolutegravir. CAB is under development as a long-acting injectable formulation for treatment of HIV-1 infection and for pre-exposure prophylaxis. We conducted an in vitro passage study of raltegravir- or elvitegravir-resistant signature mutants in the presence of CAB to characterize the resistance profile of this drug. During passage with Q148H virus, G140S arose by day 14, followed by G149A and C56S...
January 30, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29369776/successful-treatment-of-marburg-virus-with-orally-administrated-t-705-favipiravir-in-a-mouse-model
#12
Wenjun Zhu, Zirui Zhang, Shihua He, Gary Wong, Logan Banadyga, Xiangguo Qiu
Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola)...
January 21, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29360474/a-novel-flavanone-derivative-inhibits-dengue-virus-fusion-and-infectivity
#13
Pimsiri Srivarangkul, Wanchalerm Yuttithamnon, Aphinya Suroengrit, Saran Pankaew, Kowit Hengprasartporn, Thanyada Rungrotmongkol, Preecha Phuwaphriasirisarn, Kiat Ruxrungtham, Siwaporn Boonyasuppayakorn
Dengue infection is a global burden affecting millions of world population. Previous studies indicated that flavanones were potential dengue virus inhibitors. We discovered that a novel flavanone derivative, 5-hydroxy-7-methoxy-6-methylflavanone (FN5Y), inhibited DENV2 pH-dependent fusion in cell-based system with strong binding efficiency to DENV envelope protein at K (P83, L107, K128, L198), K' (T48, E49, A50, L198, Q200, L277), X' (Y138, V354, I357), and Y' (V97, R99, N103, K246) by molecular dynamic simulation...
January 19, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29357297/synergy-evaluation-of-anti-herpes-simplex-virus-type-1-and-2-compounds-acting-on-different-steps-of-virus-life-cycle
#14
Elena Criscuolo, Nicola Clementi, Nicasio Mancini, Roberto Burioni, Marco Miduri, Matteo Castelli, Massimo Clementi
Despite the clinical need of novel and safe anti-herpetic compounds effective for treating both primary infections and reactivations of Herpes Simplex Virus type 1 (HSV-1) and type 2 (HSV-2), the development of novel antivirals approved for clinical administration has been limited in the last decades to improvements of nucleoside analogues compounds. In this context, targeting different steps of the herpesvirus life cycle, including entry and cell-to-cell infection, can represent an important starting point for obtaining more efficient infection inhibition, and for overcoming both drug resistance and toxicity...
January 18, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29337166/cd163-knockout-pigs-are-fully-resistant-to-highly-pathogenic-porcine-reproductive-and-respiratory-syndrome-virus
#15
Huaqiang Yang, Jian Zhang, Xianwei Zhang, Junsong Shi, Yongfei Pan, Rong Zhou, Guoling Li, Zicong Li, Gengyuan Cai, Zhenfang Wu
Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe economic losses to current swine production worldwide. Highly pathogenic PRRSV (HP-PRRSV), originated from a genotype 2 PRRSV, is more virulent than classical PRRSV and further exacerbates the economic impact. HP-PRRSV has become the predominant circulating field strain in China since 2006. CD163 is a cellular receptor for PRRSV. The depletion of CD163 whole protein or SRCR5 region (interaction site for the virus) confers resistance to infection of several PRRSV isolates in pigs or cultured host cells...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29337165/establishment-of-intracellular-tenofovir-diphosphate-as-the-key-determinant-for-in-vitro-in-vivo-translation-of-antiviral-efficacy
#16
Bennett Ma, Aline Barth, Carolyn M McHale, Ming-Tain Lai
In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir alafenamide (TAF) revealed comparable antiviral effects with respect to the tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells (PBMCs), despite the EC50 values determined based on prodrug concentrations were nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses were in good agreement with the in vitro results, indicating intracellular TFV-DP can be employed for in vitro-in vivo translation of viral inhibition for tenofovir prodrugs...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29337164/identification-of-novel-antivirals-inhibiting-recognition-of-venezuelan-equine-encephalitis-virus-capsid-protein-by-the-importin-%C3%AE-%C3%AE-1-heterodimer-through-high-throughput-screening
#17
David R Thomas, Lindsay Lundberg, Chelsea Pinkham, Sharon Shechter, Aaron Debono, Jonathan Baell, Kylie M Wagstaff, Caroline A Hick, Kylene Kehn-Hall, David A Jans
Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the cause of multiple outbreaks resulting in extensive human and equine mortality and morbidity, there are currently no anti-VEEV therapeutics available. VEEV pathogenicity is largely dependent on targeting of the viral capsid protein (CP) to the host cell nucleus through the nuclear transporting importin (Imp) α/β1 heterodimer. Here we perform a high-throughput screen, combined with nested counterscreens to identify small molecules able to inhibit the Impα/β1:CP interaction for the first time...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29337163/utility-of-ultra-deep-sequencing-for-detection-of-varicella-zoster-virus-antiviral-resistance-mutations
#18
Mélanie Mercier-Darty, David Boutolleau, Raphaël Lepeule, Christophe Rodriguez, Sonia Burrel
We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant VZV infection initially detected by Sanger sequencing within a deeply immunocompromised heart transplant recipient. As added-value compared to Sanger analysis, UDS revealed complex dynamics of viral population under antiviral pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus affecting populations worldwide. VZV is commonly acquired in youth whose primary infection usually manifests as benign varicella (chickenpox)...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29331320/zika-dengue-and-yellow-fever-viruses-induce-differential-anti-viral-immune-responses-in-human-monocytic-and-first-trimester-trophoblast-cells
#19
Huanle Luo, Evandro R Winkelmann, Ildefonso Fernandez-Salas, Li Li, Sandra V Mayer, Rogelio Daniz-Lozano, Rosa Ma Sanchez-Casas, Nikos Vasilakis, Robert Tesh, Alan D Barrett, Scott C Weaver, Tian Wang
Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal birth defects, but the causative mechanism is incompletely understood. ZIKV shares sequence homology and early clinical manifestations with yellow fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by the same species of mosquitoes. However, YFV and DENV have been rarely reported to cause congenital diseases. Here, we compared infection with a contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and first-trimester trophoblasts (HTR-8)...
January 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29330092/a-novel-double-antigen-sandwich-elisa-for-the-species-independent-detection-of-crimean-congo-hemorrhagic-fever-virus-specific-antibodies
#20
Miriam A Sas, Loic Comtet, Fabien Donnet, Marc Mertens, Zati Vatansever, Noel Tordo, Philippe Pourquier, Martin H Groschup
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease in humans caused by the CCHF virus (CCHFV). The detection of anti-CCHFV antibodies in animals is used to reveal infection risk areas. Therefore a simple, quick and reliable multispecies assay for the detection of CCHFV-specific antibodies is needed. This work presents the development and validation of a novel CCHF double-antigen ELISA for the detection of anti-CCHFV nucleoprotein antibodies. The test requires 30 μl of serum, and results are obtained within 90 min...
January 9, 2018: Antiviral Research
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