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Antiviral Research

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https://www.readbyqxmd.com/read/28818572/ribavirin-inhibits-zika-virus-zikv-replication-in-vitro-and-suppresses-viremia-in-zikv-infected-stat1-deficient-mice
#1
Naganori Kamiyama, Ryusuke Soma, Shinya Hidano, Kei Watanabe, Hiroshi Umekita, Chiaki Fukuda, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Lucky Ronald Runtuwene, Yumako Miura, Etsuro Matsubara, Shigeru Tajima, Tomohiko Takasaki, Yuki Eshita, Takashi Kobayashi
Zika fever, a mosquito-borne infectious disease caused by Zika virus (ZIKV), is an epidemic disease for which no effective therapy has been established. The recent outbreaks of ZIKV in Brazil and French Polynesia have been linked to a considerable increase in the incidence of fetal microcephaly and other diseases such as Guillain-Barre syndrome. Because there is currently no specific therapy or vaccine, the early exploitation of a method to prevent expansion of ZIKV is a high priority. To validate commonly used antiviral drugs, we evaluated the effect of ribavirin, a drug used to treat hepatitis C with interferon-β (IFN-β), on ZIKV replication...
August 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28811186/identification-and-characterization-of-small-molecule-inhibitors-of-porcine-reproductive-and-respiratory-syndrome-virus
#2
Alyssa B Evans, Pengfei Dong, Hyelee Loyd, Jianqiang Zhang, George A Kraus, Susan Carpenter
Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound atractylodinol and demonstrated anti-PRRSV activity in vitro. However, the synthetic route was inefficient and the yield was poor...
August 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28807685/an-rna-polymerase-ii-driven-ebola-virus-minigenome-system-as-an-advanced-tool-for-antiviral-drug-screening
#3
Emily V Nelson, Jennifer R Pacheco, Adam Hume, Tessa N Cressey, Laure R Deflubé, John B Ruedas, John H Connor, Hideki Ebihara, Elke Mühlberger
Ebola virus (EBOV) causes a severe disease in humans with the potential for significant international public health consequences. Currently, treatments are limited to experimental vaccines and therapeutics. Therefore, research into prophylaxis and antiviral strategies to combat EBOV infections is of utmost importance. The requirement for high containment laboratories to study EBOV infection is a limiting factor for conducting EBOV research. To overcome this issue, minigenome systems have been used as valuable tools to study EBOV replication and transcription mechanisms and to screen for antiviral compounds at biosafety level 2...
August 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28802866/global-update-on-the-susceptibility-of-human-influenza-viruses-to-neuraminidase-inhibitors-2015-2016
#4
Larisa V Gubareva, Terry G Besselaar, Rod S Daniels, Alicia Fry, Vicki Gregory, Weijuan Huang, Aeron C Hurt, Patricia A Jorquera, Angie Lackenby, Sook-Kwan Leang, Janice Lo, Dmitriy Pereyaslov, Helena Rebelo-de-Andrade, Marilda M Siqueira, Emi Takashita, Takato Odagiri, Dayan Wang, Wenqing Zhang, Adam Meijer
Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) assessed antiviral susceptibility of 14,330 influenza A and B viruses collected by WHO-recognized National Influenza Centres (NICs) between May 2015 and May 2016. Neuraminidase (NA) inhibition assay was used to determine 50% inhibitory concentration (IC50) data for NA inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir...
August 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28789986/interferon-independent-antiviral-activity-of-25-hydroxycholesterol-in-a-teleost-fish
#5
Patricia Pereiro, Gabriel Forn-Cuní, Sonia Dios, Julio Coll, Antonio Figueras, Beatriz Novoa
Oxysterols are a family of cholesterol oxygenated derivatives with diverse roles in many biological activities and have recently been linked with the induction of a cellular antiviral state. The antiviral effects of 25-hydroxycholesterol (25HC) extend to several mammalian enveloped and non-enveloped viruses. It has been reported that the expression of the gene encoding cholesterol 25-hydroxylase (CH25H) is induced by interferons (IFNs). In this work, five ch25h genes were identified in the zebrafish (Danio rerio) genome...
August 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28780426/characterization-of-oseltamivir-resistant-influenza-virus-populations-in-immunosuppressed-patients-using-digital-droplet-pcr-comparison-with-qpcr-and-next-generation-sequencing-analysis
#6
Maxime Pichon, Alexandre Gaymard, Laurence Josset, Martine Valette, Gilles Millat, Bruno Lina, Vanessa Escuret
INTRODUCTION: The H275Y substitution in neuraminidase (NA) confers oseltamivir-resistance in A(H1N1) influenza viruses (IV). Droplet digital PCR (ddPCR) is a new technique to explore single nucleotide polymorphisms. The aim of this study was to compare the performances of reverse transcriptase (RT)-ddPCR, RT-qPCR and next generation sequencing (NGS). We also analyzed the proportions of H275Y-NA substitution for two immunosuppressed patients with sustained shedding of A(H1N1)pdm09 IV. METHODS: RT-qPCR was performed using the ABI7500 platform...
August 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28780424/the-cholesterol-transport-inhibitor-u18666a-inhibits-type-i-feline-coronavirus-infection
#7
Tomomi Takano, Misaki Endoh, Hiroaki Fukatsu, Haruko Sakurada, Tomoyoshi Doki, Tsutomu Hohdatsu
Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease in wild and domestic cats. FCoV exists in two serotypes. Type I FCoV is the dominant serotype worldwide. Therefore, it is necessary to develop antiviral drugs against type I FCoV infection. We previously reported that type I FCoV is closely associated with cholesterol throughout the viral life cycle. In this study, we investigated whether U18666A, the cholesterol synthesis and transport inhibitor, shows antiviral effects against type I FCoV...
August 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28780422/efficacy-of-a-high-potency-o1-manisa-monovalent-vaccine-against-heterologous-challenge-with-foot-and-mouth-disease-virus-of-o-sea-mya-98-lineage-in-sheep
#8
N B Singanallur, J M Pacheco, J Arzt, C Stenfeldt, G T Fosgate, L Rodriguez, W Vosloo
Potency tests for commercial oil-adjuvanted foot-and-mouth disease (FMD) vaccines are usually carried out in cattle, using a full dose (2 ml) of vaccine and homologous virus challenge. However, in sheep the recommended vaccine dose is half of the cattle dose (1 ml) and most vaccines have not been potency tested for this species, especially with heterologous viruses. To determine the efficacy of a high potency (>6PD50) FMD virus (FMDV) O1Manisa vaccine in sheep, we carried out a study using a heterologous FMDV (FMDV O/SKR/2010 - Mya-98 strain) challenge...
August 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28780425/enhanced-protection-against-experimental-junin-virus-infection-through-the-use-of-a-modified-favipiravir-loading-dose-strategy
#9
Brian B Gowen, Jonna B Westover, Eric J Sefing, Arnaud J Van Wettere, Kevin W Bailey, Luci Wandersee, Takashi Komeno, Yousuke Furuta
A collection of Old and New World arenaviruses are etiologic agents of viral hemorrhagic fever, a syndrome that features hematologic abnormalities, vascular leak, hypovolemia, and multi-organ failure. Treatment is limited to ribavirin for Lassa fever and immune plasma for Argentine hemorrhagic fever. Improved therapeutic options that are safe, more effective and widely available are needed. Here, we show that modification of favipiravir treatment to include a high-dose loading period achieves complete protection in a guinea pig model of Argentine hemorrhagic fever when treatment was initiated two days following challenge with Junin virus (JUNV)...
August 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28780423/cinnamic-acid-derivatives-inhibit-hepatitis-c-virus-replication-via-the-induction-of-oxidative-stress
#10
Ryota Amano, Atsuya Yamashita, Hirotake Kasai, Tomoka Hori, Sayoko Miyasato, Setsu Saito, Hiromasa Yokoe, Kazunori Takahashi, Tomohisa Tanaka, Teruhime Otoguro, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi
Several cinnamic acid derivatives have been reported to exhibit antiviral activity. In this study, we prepared 17 synthetic cinnamic acid derivatives and screened them to identify an effective antiviral compound against hepatitis C virus (HCV). Compound 6, one of two hit compounds, suppressed the viral replications of genotypes 1b, 2a, 3a, and 4a with EC50 values of 1.5-8.1 μM and SI values of 16.2-94.2. The effect of compound 6 on the phosphorylation of Tyr(705) in signal transducer and activator of transcription 3 (STAT3) was investigated because a cinnamic acid derivative AG490 was reported to suppress HCV replication and the activity of Janus kinase (JAK) 2...
August 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28778830/discovery-of-dapivirine-a-nonnucleoside-hiv-1-reverse-transcriptase-inhibitor-as-a-broad-spectrum-antiviral-against-both-influenza-a-and-b-viruses
#11
Yanmei Hu, Jiantao Zhang, Rami Ghassan Musharrafieh, Chunlong Ma, Raymond Hau, Jun Wang
The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy...
August 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28778831/immunogenicity-of-an-influenza-virus-vectored-vaccine-carrying-the-hepatitis-c-virus-protein-epitopes-in-mice
#12
Shaogeng Zhang, Fang Sun, Tianyu Ren, Yueqiang Duan, Hongjing Gu, Chengcai Lai, Zhaohai Wang, Peirui Zhang, Xiliang Wang, Penghui Yang
Hepatitis C virus (HCV) has a devastating impact on human health, and infections can progress into liver fibrosis, cirrhosis, and hepatocellular carcinoma. There is no effective HCV vaccine. In this study, we rescued a recombinant PR8 influenza viral vector, called rgFLU-HCVCE1E2, carrying the core and envelope glycoprotein (C/E1/E2) epitopes of HCV inserted into the influenza nonstructural protein 1 gene. The morphological characteristics of rgFLU-HCVCE1E2 and the expression of the C/E1/E2 epitopes of HCV were examined...
August 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28774800/highlights-of-the-30th-international-conference-on-antiviral-research
#13
Graciela Andrei, Kara Carter, Zlatko Janeba, Aruna Sampath, Luis M Schang, E Bart Tarbet, R Anthony Vere Hodge, Mike Bray, José A Esté
The 30th International Conference on Antiviral Research (ICAR) was held in Atlanta, GA, USA from May 18 to 21, 2017. This report provides an account of award lectures, invited keynote addresses and oral presentations during the meeting. The 2017 Gertrude Elion Memorial Lecture Award by Michael Sofia highlighted one of the most important accomplishments in recent drug discovery in antiviral research, the identification of the hepatitis C virus direct-acting antiviral sofosbuvir and new alternatives to combat hepatitis B virus (HBV) infection...
July 31, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28757394/broad-spectrum-non-nucleoside-inhibitors-for-caliciviruses
#14
Natalie E Netzler, Daniel Enosi Tuipulotu, Auda A Eltahla, Jennifer H Lun, Salvatore Ferla, Andrea Brancale, Nadya Urakova, Michael Frese, Tanja Strive, Jason M Mackenzie, Peter A White
Viruses of the Caliciviridae cause significant and sometimes lethal diseases, however despite substantial research efforts, specific antivirals are lacking. Broad-spectrum antivirals could combat multiple viral pathogens, offering a rapid solution when no therapies exist. The RNA-dependent RNA polymerase (RdRp) is an attractive antiviral target as it is essential for viral replication and lacks mammalian homologs. To focus the search for pan-Caliciviridae antivirals, the RdRp was probed with non-nucleoside inhibitors (NNIs) developed against hepatitis C virus (HCV) to reveal both allosteric ligands for structure-activity relationship enhancement, and highly-conserved RdRp pockets for antiviral targeting...
July 27, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28754258/viral-minority-variants-in-the-core-promoter-and-precore-region-identified-by-deep-sequencing-are-associated-with-response-to-peginterferon-and-adefovir-in-hbeag-negative-chronic-hepatitis-b-patients
#15
Louis Jansen, Matthijs R A Welkers, Karel A van Dort, R Bart Takkenberg, Uri Lopatin, Hans L Zaaijer, Menno D de Jong, Hendrik W Reesink, Neeltje A Kootstra
BACKGROUND AND AIM: Precore (PC) and basal core promoter (BCP) mutations are associated with responses to interferon-based treatment in HBeAg-positive chronic hepatitis B (CHB) patients. Here, we identify viral minority variants in these regions and assess association with response to peginterferon-alfa (Peg-IFN) and adefovir combination therapy. PATIENTS AND METHODS: Ultra-deep pyrosequencing analysis of the BCP and PC region was performed for 89 CHB patients (42 HBeAg-positive; 47 HBeAg-negative), at baseline and during treatment...
July 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28743447/dual-targeted-anti-tb-anti-hiv-heterodimers
#16
Liudmila Alexandrova, Sonia Zicari, Elena Matyugina, Anastasia Khandazhinskaya, Tatiana Smirnova, Sofia Andreevskaya, Larisa Chernousova, Christophe Vanpouille, Sergei Kochetkov, Leonid Margolis
HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds. These compounds constitute heterodimers of AZT, as anti-HIV molecules, and 5-arylaminouracil derivatives or 2'-deoxyuridine monophosphates analogues, as anti-TB molecules. We found that these compounds inhibit the growth of M. tuberculosis and suppress the replication of HIV in human cell cultures and human lymphoid tissues ex vivo...
July 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28739278/p38mapk-plays-a-critical-role-in-induction-of-a-pro-inflammatory-phenotype-of-retinal-m%C3%A3-ller-cells-following-zika-virus-infection
#17
Shuang Zhu, Huanle Luo, Hua Liu, Yonju Ha, Elizabeth R Mays, Ryan E Lawrence, Evandro Winkelmann, Alan D Barrett, Sylvia B Smith, Min Wang, Tian Wang, Wenbo Zhang
Zika virus (ZIKV) infection has been associated with ocular abnormalities such as chorioretinal atrophy, optic nerve abnormalities, posterior uveitis and idiopathic maculopathy. Yet our knowledge about ZIKV infection in retinal cells and its potential contribution to retinal pathology is still very limited. Here we found that primary Müller cells, the principal glial cells in the retina, expressed a high level of ZIKV entry cofactor AXL gene and were highly permissive to ZIKV infection. In addition, ZIKV-infected Müller cells exhibited a pro-inflammatory phenotype and produced many inflammatory and growth factors...
July 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28736077/replication-of-the-zika-virus-in-different-ipsc-derived-neuronal-cells-and-implications-to-assess-efficacy-of-antivirals
#18
Kristina Lanko, Kristel Eggermont, Abdulsamie Patel, Suzanne Kaptein, Leen Delang, Catherine M Verfaillie, Johan Neyts
Infections with the Zika virus (ZIKV) are responsible for congenital abnormalities and neurological disorders. We here demonstrate that ZIKV productively infects three types of human iPSC (induced pluripotent stem cells)-derived cells from the neural lineage, i.e. cortical and motor neurons as well as astrocytes. ZIKV infection results in all three cell types in the production of infectious virus particles and induces cytopathic effects (CPE). In cortical and motor neurons, an Asian isolate (PRVABC59) produced roughly 10-fold more virus than the prototypic African strain (MR766 strain)...
July 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28733114/targeting-heat-shock-factor-1-as-an-antiviral-strategy-against-dengue-virus-replication-in%C3%A2-vitro-and-in%C3%A2-vivo
#19
Tsung-Ting Tsai, Chia-Ling Chen, Cheng-Chieh Tsai, Chiou-Feng Lin
Fever onset is correlated with viremia in dengue virus (DENV) patients. Heat shock factor 1 (HSF1), a heat stress response host transcription factor, plays a crucial role in regulating multiple cellular functions, as well as the onset of infectious diseases. This study evaluated the role of HSF1 in DENV replication as a means of regulating DENV infection in vitro and in vivo. DENV infection activated HSF1 in both Ca(2+) and protein kinase A-dependent manners. Inhibiting HSF1 effectively reduced DENV replication, not only in THP-1 cells but also in primary human monocytes...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28733113/a-heterologous-prime-boost-ebola-virus-vaccine-regimen-induces-durable-neutralizing-antibody-response-and-prevents-ebola-virus-like-particle-entry-in-mice
#20
Tan Chen, Dapeng Li, Yufeng Song, Xi Yang, Qingwei Liu, Xia Jin, Dongming Zhou, Zhong Huang
Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting...
July 18, 2017: Antiviral Research
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