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Antiviral Research

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https://www.readbyqxmd.com/read/28427827/antiviral-screen-identifies-ev71-inhibitors-and-reveals-camptothecin-target-dna-topoisomerase-1-as-a-novel-ev71-host-factor
#1
Kan Xing Wu, Justin Jang-Hann Chu
Enterovirus 71 (EV71) is one of the causative agents of hand, foot and mouth disease (HFMD) associated with severe neurological disease. EV71's pathogenesis remains poorly understood and the lack of approved antiviral has led to its emergence as a clinically important neurotropic virus. The goals of this study were to: (i) identify novel anti-EV71 compounds that may serve as lead molecules for therapeutics; and (ii) investigate their targets in downstream studies. We screened a 502-compound library of highly purified natural products for anti-EV71 activities in a cell-based immunofluorescence assay that were then confirmed in viral plaque reduction assays...
April 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28414053/inhibition-effects-of-novel-polyketide-compound-ppq-b-against-influenza-a-virus-replication-by-interfering-with-the-cellular-egfr-pathway
#2
Miaomiao Wang, Shuyao Wang, Wei Wang, Yi Wang, Hui Wang, Weiming Zhu
Development of anti-influenza A virus (IAV) drugs with novel targets and low toxicity is critical for preparedness against influenza outbreaks. In the current study, our results indicated that the novel polyketide compound purpurquinone B (PPQ-B) derived from acid-tolerant fungus Penicillium purpurogenum strain JS03-21 suppressed the replication of IAV in vitro with low toxicity, and may block some stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34; PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009) virus replication in vitro, suggesting that PPQ-B possesses broad-spectrum anti-IAV activities...
April 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28412183/structure-activity-relationship-analysis-of-mitochondrial-toxicity-caused-by-antiviral-ribonucleoside-analogs
#3
Zhinan Jin, April Kinkade, Ishani Behera, Shuvam Chaudhuri, Kathryn Tucker, Natalia Dyatkina, Vivek K Rajwanshi, Guangyi Wang, Andreas Jekle, David B Smith, Leo Beigelman, Julian A Symons, Jerome Deval
Recent cases of severe toxicity during clinical trials have been associated with antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have hypothesized that the active metabolites of toxic ribonucleoside analogs, the triphosphate forms, inadvertently target human mitochondrial RNA polymerase (POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis. Others have proposed that the prodrug moiety released from the ribonucleoside analogs might instead cause toxicity. Here, we report the mitochondrial effects of several clinically relevant and structurally diverse ribonucleoside analogs including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094)...
April 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28412182/characterization-of-three-small-molecule-inhibitors-of-enterovirus-71-identified-from-screening-of-a-library-of-natural-products
#4
Guiming Li, Qianqian Gao, Shilin Yuan, Lili Wang, Ralf Altmeyer, Ke Lan, Feifei Yin, Gang Zou
Enterovirus 71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD). Infection with EV-A71 is more often associated with neurological complications in children and is responsible for the majority of fatalities, but currently there is no approved antiviral therapy for treatment. Here, we identified auraptene, formononetin, and yangonin as effective inhibitors of EV-A71 infection in the low-micromolar range from screening of a natural product library. Among them, formononetin and yangonin selectively inhibited EV-A71 while auraptene could inhibit viruses within the enterovirus species A...
April 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28408133/a-recombinant-h7n9-influenza-vaccine-with-the-h7-hemagglutinin-transmembrane-domain-replaced-by-the-h3-domain-induces-increased-cross-reactive-antibodies-and-improved-interclade-protection-in-mice
#5
Yang Wang, Jialing Wu, Chunyi Xue, Zhihui Wu, Ying Lin, Ying Wei, Xiaona Wei, Jianru Qin, Yun Zhang, Zhifen Wen, Li Chen, George Dacai Liu, Yongchang Cao
Influenza A H7N9 virus is the latest emerging pandemic threat, and has rapidly diverged into three clades, demanding a H7N9 virus vaccine with broadened protection against unmatched strains. Hemagglutinin (HA)-based structural design approaches for stabilizing HA proteins have provided excitingly promising results. However, none of the HA-based structural design approaches has been applied to a recombinant replicative influenza virus. Here we report that our HA-based structural design approach is a first in the field to generate a recombinant replicative H7N9 virus (H7N9-53TM) showing broadened protection...
April 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28404225/herpes-simplex-virus-type-1-abrogates-the-antiviral-activity-of-ch25h-via-its-virion-host-shutoff-protein
#6
Hongjuan You, Hui Yuan, Wenkun Fu, Chenhe Su, Wei Wang, Tong Cheng, Chunfu Zheng
Cholesterol 25-hydroxylase (Ch25h) is an interferon-inducible protein, and recent studies have demonstrated that it inhibited the replication of many enveloped viruses. However, in this study, we found that cells infected with wild-type (WT) HSV-1 reduced the expression of Ch25h, and ectopic expression of Ch25h could not inhibit the replication of WT-HSV-1. By screening assay, HSV-1 UL41 protein was found to down-regulate the expression of Ch25h. In addition, UL41 abrogated the antiviral activity of Ch25h via degrading its mRNA...
April 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28400201/inhibitors-of-dual-specificity-tyrosine-phosphorylation-regulated-kinases-dyrk-exert-a-strong-anti-herpesviral-activity
#7
Corina Hutterer, Jens Milbradt, Stuart Hamilton, Mirko Zaja, Johann Leban, Christophe Henry, Daniel Vitt, Mirjam Steingruber, Eric Sonntag, Isabel Zeitträger, Hanife Bahsi, Thomas Stamminger, William Rawlinson, Stefan Strobl, Manfred Marschall
Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of (val)ganciclovir therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy of antiviral treatment is based on the exploitation of cell-directed signaling, e. g. pathways with a known relevance for carcinogenesis and tumor drug development. Here we describe a principle for putative antiviral drugs based on targeting dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs)...
April 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28396205/entry-inhibition-of-hsv-1-and-2-protects-mice-from-viral-lethal-challenge
#8
Nicola Clementi, Elena Criscuolo, Francesca Cappelletti, Paola Quaranta, Mauro Pistello, Roberta A Diotti, Giuseppe A Sautto, Alexander W Tarr, Federico Mailland, Daniela Concas, Roberto Burioni, Massimo Clementi, Nicasio Mancini
The present study focused on inhibition of HSV-1 and -2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu-mAb#33) was identified that could neutralise both HSV-1 and -2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell-free viruses and cell-to-cell virus transmission was also assessed...
April 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28392420/efficacy-of-delayed-brincidofovir-treatment-against-a-lethal-rabbitpox-virus-challenge-in-new-zealand-white-rabbits
#9
Irma M Grossi, Scott A Foster, Melicia R Gainey, Robert T Krile, John A Dunn, Thomas Brundage, Jody M Khouri
In the event of a bioterror attack with variola virus (smallpox), exposure may only be identified following onset of fever. To determine if antiviral therapy with brincidofovir (BCV; CMX001) initiated at, or following, onset of fever could prevent severe illness and death, a lethal rabbitpox model was used. BCV is in advanced development as an antiviral for the treatment of smallpox under the US Food and Drug Administration's 'Animal Rule'. This pivotal study assessed the efficacy of immediate versus delayed treatment with BCV following onset of symptomatic disease in New Zealand White rabbits intradermally inoculated with a lethal rabbitpox virus (RPXV), strain Utrecht...
April 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28392419/early-phase-dynamics-of-traceable-mcherry-fluorescent-protein-carrying-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells-transplanted-nod-scid-jak3-mice
#10
Nobuyo Higashi-Kuwata, Hiromi Ogata-Aoki, Shin-Ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Tatsuyoshi Kawamura, Hironobu Ihn, Hisataka Kobayashi, Seiji Okada, Hiroaki Mitsuya
We attempted to elucidate early-phase dynamics of HIV-1 infection using replication-competent, red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL (HIVJR-FL(mC)) and NOD/SCID/Jak3(-/-) mice transplanted with Individual-A's human peripheral blood mononuclear cells (hPBMC)(hNOJ mice). On day 7 following HIVJR-FL(mC) inoculation, mCherry-signal-emitting infection foci were readily identified in the subserosa of 10 of 10 HIVJR-FL(mC)-inoculated hNOJ mice, although infection foci were not located without the mCherry signal in unlabeled HIV-1JR-FL-inoculated mice (n = 6)...
April 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28390873/chikungunya-virus-nsp4-rna-dependent-rna-polymerase-core-domain-displays-detergent-sensitive-primer-extension-and-terminal-adenylyltransferase-activities
#11
Ming Wei Chen, Yaw Bia Tan, Jie Zheng, Yongqian Zhao, Bee Ting Lim, Tobias Cornvik, Julien Lescar, Lisa Fong Poh Ng, Dahai Luo
Chikungunya virus (CHIKV) is an important arboviral infectious agent in tropical and subtropical regions, often causing persistent and debilitating disease. The viral enzyme non-structural protein 4 (nsP4), as RNA-dependent RNA polymerase (RdRP), catalyzes the formation of negative-sense, genomic and subgenomic viral RNAs. Here we report a truncated nsP4 construct that is soluble, stable and purified recombinantly from Escherichia coli. Sequence analyses and homology modelling indicate that all necessary RdRP elements are included...
April 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28390872/the-role-of-epidermal-growth-factor-receptor-egfr-signaling-in-sars-coronavirus-induced-pulmonary-fibrosis
#12
REVIEW
Thiagarajan Venkataraman, Matthew B Frieman
Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection...
April 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28389142/efficacy-of-antibody-based-therapies-against-middle-east-respiratory-syndrome-coronavirus-mers-cov-in-common-marmosets
#13
Neeltje van Doremalen, Darryl Falzarano, Tianlei Ying, Emmie de Wit, Trenton Bushmaker, Friederike Feldmann, Atsushi Okumura, Yanping Wang, Dana P Scott, Patrick W Hanley, Heinz Feldmann, Dimiter S Dimitrov, Vincent J Munster
Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation...
April 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28389141/luteolin-restricts-dengue-virus-replication-through-inhibition-of-the-proprotein-convertase-furin
#14
Minhua Peng, Satoru Watanabe, Kitti Wing Ki Chan, Qiuyan He, Ya Zhao, Zhongde Zhang, Xiaoping Lai, Dahai Luo, Subhash G Vasudevan, Geng Li
The increasing prevalence of dengue fever in the Indian sub-continent and Southern China is a major public health concern. There is currently an approved tetravalent vaccine available in a handful of countries for protection from dengue infection, but its efficacy against dengue virus (DENV) serotype 2 is not ideal and its overall performance in children under 9 years of age is poor. In many of the dengue afflicted countries-traditional medicine is widely used as a panacea for illnesses and here we describe the systematic evaluation of a natural product, luteolin, originating from the "heat clearing" class of herbs...
April 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28385500/successful-strategies-implemented-towards-the-elimination-of-canine-rabies-in-the-western-hemisphere
#15
REVIEW
Andres Velasco-Villa, Luis E Escobar, Anthony Sanchez, Mang Shi, Daniel G Streicker, Nadia F Gallardo-Romero, Fernando Vargas-Pino, Veronica Gutierrez-Cedillo, Inger Damon, Ginny Emerson
Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. This article reviews progress in eliminating canine rabies from the Western Hemisphere. After briefly summarizing the history of control efforts and describing the approaches listed above, we note that programs in some countries have been hindered by societal attitudes and severe economic disparities, which underlines the need to discuss measures that will be required to complete the elimination of canine rabies throughout the region...
April 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28377100/the-mek-inhibitor-ci-1040-displays-a-broad-anti-influenza-virus-activity-in%C3%A2-vitro-and-provides-a-prolonged-treatment-window-compared-to-standard-of-care-in%C3%A2-vivo
#16
Emanuel Haasbach, Christin Müller, Christina Ehrhardt, Andre Schreiber, Stephan Pleschka, Stephan Ludwig, Oliver Planz
Influenza viruses (IV) continue to pose an imminent threat to human welfare. Yearly re-occurring seasonal epidemic outbreaks and pandemics with high mortality can occur. Besides vaccination against a limited number of viral strains only a few antiviral drugs are available, which are losing their effectiveness as more and more IV strains become resistant. Thus, new antiviral approaches that omit IV resistance are urgently needed. Here, the dependency on the cellular Raf/MEK/ERK signaling pathway for IV replication opens a new perspective...
April 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28365456/mir-21-promotes-dengue-virus-serotype-2-replication-in-hepg2-cells
#17
Sitthichai Kanokudom, Tirayut Vilaivan, Nitwara Wikan, Chutima Thepparit, Duncan R Smith, Wanchai Assavalapsakul
Infection with the mosquito transmitted dengue virus (DENV) remains a significant worldwide public health problem. While the majority of infections are asymptomatic, infection can result in a range of symptoms. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through repression or degradation of mRNAs. To understand the contribution of miRNAs to DENV 2 replication, we screened a number of candidate miRNAs for variations in expression levels during DENV 2 infection of HepG2 (liver) cells...
March 30, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28365457/the-history-of-rabies-in-the-western-hemisphere
#18
REVIEW
Andres Velasco-Villa, Matthew R Mauldin, Mang Shi, Luis E Escobar, Nadia F Gallardo-Romero, Inger Damon, Victoria A Olson, Daniel G Streicker, Ginny Emerson
Before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the Western Hemisphere. However, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first European colonizers, rabies virus was likely present only in bats and skunks. Canine rabies was either rare or absent among domestic dogs of Native Americans, and first arrived when many new dog breeds were imported during the period of European colonization...
March 29, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28363735/evolution-of-tenofovir-resistant-hiv-1-isolates-exposed-to-tenofovir-alafenamide-dose-escalation
#19
Stephanie Cox, Nicolas Margot, Renee Ram, Audun Johnson, Michael Miller, Christian Callebaut
Resistance selection experiments using HIV-1 isolates harboring pre-existing tenofovir (TFV)-resistance (K65R, 3TAMs, and Q151M complex) were carried out with the novel tenofovir prodrug tenofovir alafenamide (TAF) as well as with tenofovir (TFV), to investigate the potential for additional resistance development in the presence of TAF or TFV. Extended resistance selection of these TFV resistance associated mutations (RAMs)-containing viruses with TAF or TFV did not lead to the accumulation of additional known RAMs, or significant additional phenotypic resistance, after 6 months in culture...
March 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28359840/samhd1-is-active-in-cycling-cells-permissive-to-hiv-1-infection
#20
Roger Badia, Maria Pujantell, Javier Torres-Torronteras, Luis Menéndez-Arias, Ramón Martí, Albert Ruzo, Eduardo Pauls, Bonaventura Clotet, Ester Ballana, José A Esté, Eva Riveira-Muñoz
SAMHD1 is a triphosphohydrolase that restricts HIV-1 by limiting the intracellular dNTP pool required for reverse transcription. Although SAMHD1 is expressed and active/unphosphorylated in most cell lines, its restriction activity is thought to be relevant only in non-cycling cells. However, an in depth evaluation of SAMHD1 function and relevance in cycling cells is required. Here, we show that SAMHD1-induced degradation by HIV-2 Vpx affects the dNTP pool and HIV-1 replication capacity in the presence of the 3'-azido-3'-deoxythymidine (AZT) in cycling cells...
March 28, 2017: Antiviral Research
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