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Antiviral Research

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https://www.readbyqxmd.com/read/29051080/antiviral-activity-of-fenretinide-against-zika-virus
#1
Jared D Pitts, Pi-Chun Li, Melissanne de Wispelaere, Priscilla L Yang
The rapid spread of Zika virus (ZIKV) in recent years has highlighted the severe diseases associated with ZIKV infection, such as Guillain-Barré syndrome in adults and microcephaly in newborns. Yet, no vaccines or antivirals currently exist to prevent or treat ZIKV infection. We and others have previously identified N-(4-hydroxyphenyl) retinamide (fenretinide or 4-HPR) as an antiviral compound that inhibits dengue virus 2 (DV2) and other flaviviruses by limiting the steady-state accumulation of viral RNA. Here we show that 4-HPR potently inhibits Zika virus (ZIKV) in mammalian cell culture and significantly reduces both serum viremia and brain viral burden in a murine model of ZIKV infection...
October 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29037976/characterization-of-a-dengue-ns4b-inhibitor-originating-from-an-hcv-small-molecule-library
#2
Ilane Hernandez-Morales, Peggy Geluykens, Marleen Clynhens, Rudy Strijbos, Olivia Goethals, Sarah Megens, Nick Verheyen, Stefaan Last, David McGowan, Erwin Coesemans, Benoît De Boeck, Bart Stoops, Benoit Devogelaere, Frederik Pauwels, Koen Vandyck, Jan Martin Berke, Pierre Raboisson, Kenneth Simmen, Pedro Lory, Marnix Van Loock
Dengue is the most important mosquito-transmitted viral disease and a major global health concern. Over the last decade, dengue virus (DENV) drug discovery and development has intensified, however, this has not resulted in approved DENV-specific antiviral treatments yet. DENV and hepatitis C virus (HCV) belong to the same Flaviviridae family and, in contrast to DENV, antiviral treatments for HCV have been licensed. Therefore, applying the knowledge gained on anti-HCV drugs may foster the discovery and development of dengue antiviral drugs...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29037975/modular-cell-based-platform-for-high-throughput-identification-of-compounds-that-inhibit-a-viral-interferon-antagonist-of-choice
#3
Andri Vasou, Christina Paulus, Janina Narloch, Zoe O Gage, Marie-Anne Rameix-Welti, Jean-François Eléouët, Michael Nevels, Richard E Randall, Catherine S Adamson
Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets...
October 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29032206/divalent-copper-complexes-as-influenza-a-m2-inhibitors
#4
Nathan A Gordon, Kelly L McGuire, Spencer K Wallentine, Gregory A Mohl, Jonathan D Lynch, Roger G Harrison, David D Busath
New M2 blockers effective against the ubiquitous amantadine-resistant S31N M2 mutation in influenza A are needed. Six copper complexes, 2, 4, 6, 8, 9, and 10, were synthesized and found to block both wild type and S31N M2. Free Cu(2+) also blocks M2 S31N but not S31N/H37A. The copper complexes do not block M2 H37A (either S31 or S31N). The complexes were effective against three influenza A strains in cell-culture assays, but less toxic to cells than CuCl2. For example 4, Cu(cyclooctylamineiminodiacetate), which was stable at pH > 4 in the buffers used, had an EC50 against A/Calif/07/2009 H1N1 of 0...
October 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29031833/structure-based-drug-design-for-envelope-protein-e2-uncovers-a-new-class-of-bovine-viral-diarrhea-inhibitors-that-block-virus-entry
#5
María José Pascual, Fernando Merwaiss, Emilse Leal, María Eugenia Quintana, Alejandra V Capozzo, Claudio N Cavasotto, Mariela Bollini, Diego E Alvarez
Antiviral targeting of virus envelope proteins is an effective strategy for therapeutic intervention of viral infections. Here, we took a computer-guided approach with the aim of identifying new antivirals against the envelope protein E2 of bovine viral diarrhea virus (BVDV). BVDV is an enveloped virus with an RNA genome responsible for major economic losses of the cattle industry worldwide. Based on the crystal structure of the envelope protein E2, we defined a binding site at the interface of the two most distal domains from the virus membrane and pursued a hierarchical docking-based virtual screening search to identify small-molecule ligands of E2...
October 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29024767/modulation-of-proteolytic-polyprotein-processing-by-coxsackievirus-mutants-resistant-to-inhibitors-targeting-phosphatidylinositol-4-kinase-iii%C3%AE-or-oxysterol-binding-protein
#6
Heyrhyoung Lyoo, Cristina M Dorobantu, Hilde M van der Schaar, Frank J M van Kuppeveld
Enteroviruses (e.g. poliovirus, coxsackievirus, and rhinovirus) require several host factors for genome replication. Among these host factors are phosphatidylinositol-4-kinase IIIβ (PI4KB) and oxysterol binding protein (OSBP). Enterovirus mutants resistant to inhibitors of PI4KB and OSBP were previously isolated, which demonstrated a role of single substitutions in the non-structural 3A protein in conferring resistance. Besides the 3A substitutions (i.e., 3A-I54F and 3A-H57Y) in coxsackievirus B3 (CVB3), substitution N2D in 2C was identified in each of the PI4KB-inhibitor resistant CVB3 pools, but its possible benefit has not been investigated yet...
October 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29024766/protective-effect-of-an-alpha-7-nicotinic-acetylcholine-receptor-agonist-against-enterovirus-71-infection-in-neuronal-cells
#7
FengXia Song, LinQin Zhao, RuNan Zhu, QinWei Song, Jie Deng, Run Tian, Fang Wang, Yuan Qian
Enterovirus 71, as one of the dominant pathogens associated with severe hand, foot, and mouth disease, has been well reported to trigger severe neurological symptoms among young children over the last decade, particularly among children in the Asia-Pacific region. To date, no effective antiviral agent has been developed for the treatment of severe enterovirus 71 infection. PNU-282987, a selective alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist, has been reported to have a neuroprotective effect by participating in inflammatory regulation in previous studies...
October 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29024765/identification-of-2-deoxy-2-fluorocytidine-as-a-potent-inhibitor-of-crimean-congo-hemorrhagic-fever-virus-replication-using-a-recombinant-fluorescent-reporter-virus
#8
Stephen R Welch, Florine E M Scholte, Mike Flint, Payel Chatterjee, Stuart T Nichol, Éric Bergeron, Christina F Spiropoulou
Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne orthonairovirus, causes a severe hemorrhagic disease in humans (Crimean-Congo hemorrhagic fever, CCHF). Currently, no vaccines are approved to prevent CCHF; treatment is limited to supportive care and the use of ribavirin, the therapeutic benefits of which remain unclear. CCHF is part of WHO's priority list of infectious diseases warranting further research and development. To aid in the identification of new antiviral compounds, we generated a recombinant CCHFV expressing a reporter protein, allowing us to quantify virus inhibition by measuring the reduction in fluorescence in infected cells treated with candidate compounds...
October 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/29017779/targeted-inhibition-of-hantavirus-replication-and-intracranial-pathogenesis-by-a-chimeric-protein-delivered-sirna
#9
Jie Yang, Ji-Feng Sun, Ting-Ting Wang, Xiao-Hong Guo, Jun-Xia Wei, Lin-Tao Jia, An-Gang Yang
Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the encoding sequences of HV strain 76-118, and validated their inhibitory role in virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein, 3G1-Cκ-tP, consisting of a single-chain antibody fragment (3G1) against the HV surface envelop glycoprotein, the constant region of human immunoglobulin κ chain (Cκ), and truncated protamine (amino acids 8-29, tP), was further generated...
October 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28993161/new-class-of-early-stage-enterovirus-inhibitors-with-a-novel-mechanism-of-action
#10
Yipeng Ma, Rana Abdelnabi, Leen Delang, Mathy Froeyen, Walter Luyten, Johan Neyts, Carmen Mirabelli
4-dimethylamino benzoic acid (compound 12, synonym: 4EDMAB) was identified as an in vitro inhibitor of Coxsackie virus B3 (CVB3) replication in CPE-based assays (EC50 of 9.1 ± 1.5 μM). Next, the activity of twenty-three analogues was assessed, their structure-activity relationship was deduced and a more potent analogue was identified (EC50 of 2.6 ± 0.5 μM). The antiviral activity of 4EDMAB was further confirmed by quantifying viral RNA yield. Time-of-drug-addition assay revealed that 4EDMAB exerts its antiviral activity at the early stages of virus replication...
October 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28988797/altered-expression-of-interferon-stimulated-genes-is-strongly-associated-with-therapeutic-outcomes-in-hepatitis-b-virus-infection
#11
Meifang Han, Yong Li, Wenyu Wu, Yuanya Zhang, Weiming Yan, Xiaoping Luo, Qin Ning
Our previous OSST study shows that switching to pegylated interferon (Peg-IFN)-α2a results in higher rates of response hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) loss at the end of treatment, compared with nucleot(s)ide analogues (NAs) monotherapy in long term NA-treated chronic hepatitis B (CHB) patients. In order to characterize the correlation between Peg-IFN-α antiviral effect and IFN-inducing signaling in CHB patients who switched to Peg-IFN from long time entecavir (ETV) treatment, we investigated the dynamic expression of interferon-stimulated genes (ISGs), including STAT1, MX, and a negative regulatory factor, suppressor of cytokine signaling 3(SOCS3), which negatively regulate IFN JAK-STAT signaling pathway by interacting with STAT1 and STAT2, in peripheral blood and paired liver samples, obtained from 54 CHB patients enrolled in a clinical trial, OSST study...
October 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28986103/the-susceptibility-of-circulating-human-influenza-viruses-to-tizoxanide-the-active-metabolite-of-nitazoxanide
#12
Danielle Tilmanis, Carel van Baalen, Ding Yuan Oh, Jean-Francois Rossignol, Aeron C Hurt
Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide...
October 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28982551/a-cell-based-high-throughput-screening-assay-for-the-discovery-of-cgas-sting-pathway-agonists
#13
Bowei Liu, Liudi Tang, Xiaohui Zhang, Julia Ma, Mohit Sehgal, Junjun Cheng, Xuexiang Zhang, Yan Zhou, Yanming Du, John Kulp, Ju-Tao Guo, Jinhong Chang
Stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that serves as a molecular hub for activation of interferon and inflammatory cytokine response by multiple cellular DNA sensors. Not surprisingly, STING has been demonstrated to play an important role in host defense against microorganisms and pharmacologic activation of STING is considered as an attractive strategy to treat viral diseases and boost antitumor immunity. In light of this we established a HepAD38-derived reporter cell line that expresses firefly luciferase in response to the activation of cyclic GMP-AMP synthase (cGAS)-STING pathway for high throughput screening (HTS) of small molecular human STING agonists...
October 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28974385/inhibition-of-rubella-virus-replication-by-the-broad-spectrum-drug-nitazoxanide-in-cell-culture-and-in-a-patient-with-a-primary-immune-deficiency
#14
Ludmila Perelygina, Timo Hautala, Mikko Seppänen, Adebola Adebayo, Kathleen E Sullivan, Joseph Icenogle
Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been recently shown to have broad-spectrum antiviral activities. Here we found that empiric 2-month therapy with oral NTZ was associated in the decline/elimination of RV antigen from lesions in a PID patient with RV positive granulomas, while peginterferon treatment had no effect...
September 30, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28965916/inhibition-of-human-cytomegalovirus-replication-by-tricin-is-associated-with-depressed-ccl2-expression
#15
Yumiko Akai, Hidetaka Sadanari, Masaya Takemoto, Noboru Uchide, Tohru Daikoku, Naofumi Mukaida, Tsugiya Murayama
We previously reported that treatment with tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virion production and HCMV replication in human embryonic lung fibroblast (HEL) cells. Moreover, we recently demonstrated that HCMV infection can increase the expression of CC-motif ligand 2 (CCL2/MCP-1) and of CCR2, a CCL2-specific receptor, effects that can in turn enhance HCMV infection and replication. Hence, we here examined whether the CCL2-CCR2 axis is involved in the anti-HCMV effects of tricin in HEL cells...
September 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28965915/interplay-between-dengue-virus-and-toll-like-receptors-rig-i-mda5-and-micrornas-implications-for-pathogenesis
#16
REVIEW
Silvio Urcuqui-Inchima, Jesús Cabrera, Anne-Lise Haenni
A growing body of evidence has demonstrated the role of components of innate immunity, including Toll-like receptors (TLRs), the retinoic acid-inducible gene I/melanoma-differentiation factor 5 (RIG-I/MDA5) and microRNAs (miRNAs) in the recognition of dengue virus (DENV) or its components by infected cells. TLR3, TLR7/8 and RIG-I/MDA5 sense genomic RNA or dsRNA, the product of an intermediate step of DENV replication, activating intracellular pathways leading to the production of antiviral effectors, including interferon and pro-inflammatory cytokines...
September 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28958921/ifna2-p-ala120thr-impairs-the-inhibitory-activity-of-interferon-%C3%AE-2-against-the-hepatitis-b-virus-through-altering-its-binding-to-the-receptor
#17
Chuming Chen, Xiang Zhu, Wenxiong Xu, Fangji Yang, Genglin Zhang, Lina Wu, Yongyuan Zheng, Zhiliang Gao, Chan Xie, Liang Peng
BACKGROUND: Our previous study found that a rare genetic mutation IFNA2p.Ala120Thr affects the structure of IFN-α2 and contributes to increased host susceptibility to CHB. However, the way in which the single amino acid residue mutation affects IFN-α2 activity is unclear. The purpose of this research was to investigate the effects and mechanisms of IFNA2p.Ala120Thr on IFN-α2 activity. METHODS: Plasmid transfection of BL-21 was used to construct both wild type IFNA2 (wt) and p...
September 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28958920/antiviral-treatment-efficiently-inhibits-chikungunya-virus-infection-in-the-joints-of-mice-during-the-acute-but-not-during-the-chronic-phase-of-the-infection
#18
Rana Abdelnabi, Dirk Jochmans, Erik Verbeken, Johan Neyts, Leen Delang
Favipiravir (T-705) is a broad spectrum antiviral which has been approved in Japan for the treatment of severe influenza virus infections. We reported earlier that favipiravir inhibits the in vitro replication of CHIKV and protects against disease progression in CHIKV-infected immunodeficient mice. We here explored whether favipiravir is also able to inhibit CHIKV replication in the joints of mice either when treatment is initiated during the acute or during the chronic phase of the infection. To this end, C57BL/6J mice were infected with CHIKV in the left hind footpad and treatment with favipiravir (300 mg/kg/day, orally) was either given from day 0 to day 3 post-infection (p...
September 25, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28947234/recombinant-hemagglutinin-proteins-formulated-in-a-novel-pelc-cpg-adjuvant-for-h7n9-subunit-vaccine-development
#19
Ting-Hsuan Chen, Ying-Yu Liu, Jia-Tsrong Jan, Ming-Hsi Huang, Maureen Spearman, Michael Butler, Suh-Chin Wu
Humans infected with H7N9 avian influenza viruses can result in severe pneumonia and acute respiratory syndrome with an approximately 40% mortality rate, and there is an urgent need to develop an effective vaccine to reduce its pandemic potential. In this study, we used a novel PELC/CpG adjuvant for recombinant H7HA (rH7HA) subunit vaccine development. After immunizing BALB/c mice intramuscularly, rH7HA proteins formulated in this adjuvant instead of an alum adjuvant elicited higher IgG, hemagglutination-inhibition, and virus neutralizing antibodies in sera; induced higher numbers of H7HA-specific IFN-γ-secreting T cells and antibody secreting cells in spleen; and provided improved protection against live virus challenges...
September 22, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28941982/immune-efficacy-of-an-adenoviral-vector-based-swine-influenza-vaccine-against-antigenically-distinct-h1n1-strains-in-mice
#20
Yunpu Wu, Dawei Yang, Bangfeng Xu, Wenhua Liang, Jinyu Sui, Yan Chen, Huanliang Yang, Hualan Chen, Ping Wei, Chuanling Qiao
Avian-like H1N1 swine influenza viruses are prevalent in pigs and have occasionally crossed the species barrier and infected humans, which highlights the importance of preventing swine influenza. Human adenovirus serotype 5 (Ad5) has been tested in human influenza vaccine clinical trials and has exhibited a reliable safety profile. Here, we generated a replication-defective, recombinant adenovirus (designated as rAd5-avH1HA) expressing the hemagglutinin gene of an avian-like H1N1 virus (A/swine/Zhejiang/199/2013, ZJ/199/13)...
September 20, 2017: Antiviral Research
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