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Antiviral Research

A Coetzer, A H Kidane, M Bekele, A D Hundera, E G Pieracci, M L Shiferaw, R Wallace, L H Nel
The Stepwise Approach towards Rabies Elimination (SARE) tool was developed through a joint effort of the Food and Agriculture Organization (FAO) of the United Nations and the Global Alliance for Rabies Control (GARC), to provide a standard mechanism for countries to assess their rabies situation and measure progress in eliminating the disease. Because the African continent has the highest per capita death rate from rabies, and Ethiopia is estimated to have the second largest number of rabies deaths of all African countries, Ethiopia undertook a self-assessment by means of the Stepwise Approach towards Rabies Elimination (SARE) tool...
October 13, 2016: Antiviral Research
Alexey Martyushev, Shinji Nakaoka, Kei Sato, Takeshi Noda, Shingo Iwami
Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals...
October 12, 2016: Antiviral Research
Benjamin W Neuman
Replication of eukaryotic positive-stranded RNA viruses is usually linked to the presence of membrane-associated replicative organelles. The purpose of this review is to discuss the function of proteins responsible for formation of the coronavirus replicative organelle. This will be done by identifying domains that are conserved across the order Nidovirales, and by summarizing what is known about function and structure at the level of protein domains.
October 12, 2016: Antiviral Research
Yu-Ming Wang, Jeng-Wei Lu, Chang-Chi Lin, Yuan-Fan Chin, Tzong-Yuan Wu, Liang-In Lin, Zheng-Zong Lai, Szu-Cheng Kuo, Yi-Jung Ho
Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro...
October 11, 2016: Antiviral Research
Yi Zhang, Shoufeng Zhang, Lietao Li, Rongliang Hu, Haixiang Lin, Hua Liu, Fang Liu, Hui Shao, Yuan Liu
Most reported vaccination failures among rabies-exposed patients were due to fail to timely co-administer rabies immunoglobulin (RIG). Considering that such protection failure might be caused by low antigen titers in the vaccine, scientists improved antigen titers to 4.0 IU or even higher, yet the failure remained. Therefore, it becomes vital to develop more efficacious vaccine against rabies. In our evaluation of a novel PIKA rabies vaccine, we used multiple animal models (beagles, golden hamsters and Kunming mice) to mimic post-exposure scenarios...
October 11, 2016: Antiviral Research
Jason R Wilson, Zhu Guo, Adrian Reber, Ram P Kamal, Nedzad Music, Shane Gansebom, Yaohui Bai, Min Levine, Paul Carney, Wen-Pin Tzeng, James Stevens, Ian A York
Zoonotic A(H7N9) avian influenza viruses emerged in China in 2013 and continue to be a threat to human public health, having infected over 800 individuals with a mortality rate approaching 40%. Treatment options for people infected with A(H7N9) include the use of neuraminidase (NA) inhibitors. However, like other influenza viruses, A(H7N9) can become resistant to these drugs. The use of monoclonal antibodies is a rapidly developing strategy for controlling influenza virus infection. Here we generated a murine monoclonal antibody (3c10-3) directed against the NA of A(H7N9) and show that prophylactic systemic administration of 3c10-3 fully protected mice from lethal challenge with wild-type A/Anhui/1/2013 (H7N9)...
October 3, 2016: Antiviral Research
Jessica R Spengler, Agustín Estrada-Peña, Aura R Garrison, Connie Schmaljohn, Christina F Spiropoulou, Éric Bergeron, Dennis A Bente
This article provides a definitive review of experimental studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus (CCHFV), the etiologic agent of Crimean-Congo hemorrhagic fever (CCHF), beginning with the first recognized outbreak of the human disease in Crimea in 1944. Published reports by researchers in the former Soviet Union, Bulgaria, South Africa, and other countries where CCHF has been observed show that CCHFV is maintained in nature in a tick-vertebrate-tick enzootic cycle...
October 3, 2016: Antiviral Research
Gaofeng Lu, Juan Antonio Villa, Maureen J Donlin, Tiffany C Edwards, Xiaohong Cheng, Richard F Heier, Marvin J Meyers, John E Tavis
Hepatitis B virus (HBV) causes hepatitis, cirrhosis, liver failure, and liver cancer, but the current therapies that employ either nucelos(t)ide analogs or (pegylated)interferon α do not clear the infection in the large majority of patients. Inhibitors of the HBV ribonuclease H (RNaseH) that are being developed with the goal of producing anti-HBV drugs are promising candidates for use in combination with the nucleos(t)ide analogs to improve therapeutic efficacy. HBV is genetically very diverse, with at least 8 genotypes that differ by ≥8% at the sequence level...
September 28, 2016: Antiviral Research
Elisabeth A Pitt, Pranay Dogra, Ravi S Patel, Angela Williams, Jonathan S Wall, Tim E Sparer
Human cytomegalovirus (HCMV) infection in utero can lead to congenital sensory neural hearing loss and mental retardation. Reactivation or primary infection can increase the morbidity and mortality in immune suppressed transplant recipients and AIDS patients. The current standard of care for HCMV disease is nucleoside analogs, which can be nephrotoxic. In addition resistance to current treatments is becoming increasingly common. In an effort to develop novel CMV treatments, we tested the effectiveness of the D-form of a novel heparan sulfate binding peptide, p5RD, at reducing infection of ganciclovir (GCV) resistant HCMVs in vitro and MCMV in vivo...
September 25, 2016: Antiviral Research
Baptiste Martin, Thomas Hoenen, Bruno Canard, Etienne Decroly
This review focuses on the recent progress in our understanding of filovirus protein structure/function and its impact on antiviral research. Here we focus on the surface glycoprotein GP1,2 and its different roles in filovirus entry. We first describe the latest advances on the characterization of GP gene-overlapping proteins sGP, ssGP and Δ-peptide. Then, we compare filovirus surface GP1,2 proteins in terms of structure, synthesis and function. As they bear potential in drug-design, the discovery of small organic compounds inhibiting filovirus entry is a currently very active field...
September 14, 2016: Antiviral Research
Firas El Chaer, Nobuyoshi Mori, Dimpy Shah, Nora Oliver, Emily Wang, Anna Jan, Vi Doan, Frank Tverdek, Jean Tayar, Ella Ariza-Heredia, Roy F Chemaly
Cytomegalovirus (CMV) reactivation is a clinically significant complication in hematopoietic stem cell transplant (HCT) recipients. Alternative therapy for multidrug-resistant CMV is limited and often fails. Leflunomide has been used to treat resistant CMV infections, however, data on efficacy, safety, and guidance for therapeutic drug level monitoring are lacking. In this report, we describe 3 HCT recipients with multi-drug resistant CMV infections who received leflunomide as adjuvant and salvage therapy. The therapeutic effect of leflunomide as an anti-CMV agent based on virologic responses and therapeutic drug monitoring were evaluated...
September 1, 2016: Antiviral Research
Mariano A Garcia-Blanco, Subhash G Vasudevan, Shelton S Bradrick, Christopher Nicchitta
Upon release of the ∼11 kb single-stranded positive polarity dengue virus genomic RNA (gRNA) into the cytoplasm of an infected cell, it serves as the template for translation of the viral polyprotein, which is cleaved into three structural and seven non-structural proteins. The structural organization of the viral replication complex and RNA is not known but it is increasingly becoming evident that the viral gRNA and replication intermediates adopt unique structural features and localize to discrete regions in the infected cell...
October 2016: Antiviral Research
Angela Corona, Francesco Saverio di Leva, Giuseppe Rigogliuso, Luca Pescatori, Valentina Noemi Madia, Frederic Subra, Olivier Delelis, Francesca Esposito, Marta Cadeddu, Roberta Costi, Sandro Cosconati, Ettore Novellino, Roberto di Santo, Enzo Tramontano
HIV-1 integrase (IN) inhibitors are one of the most recent innovations in the treatment of HIV infection. The selection of drug resistance viral strains is however a still open issue requiring constant efforts to identify new anti-HIV-1 drugs. Pyrrolyl diketo acid (DKA) derivatives inhibit HIV-1 replication by interacting with the Mg(2+) cofactors within the HIV-1 IN active site or within the HIV-1 reverse-transcriptase associated ribonuclease H (RNase H) active site. While the interaction mode of pyrrolyl DKAs with the RNase H active site has been recently reported and substantiated by mutagenesis experiments, their interaction within the IN active site still lacks a detailed understanding...
October 2016: Antiviral Research
Delia Tarantino, Rolando Cannalire, Eloise Mastrangelo, Romina Croci, Gilles Querat, Maria Letizia Barreca, Martino Bolognesi, Giuseppe Manfroni, Violetta Cecchetti, Mario Milani
RNA dependent RNA polymerases (RdRp) are essential enzymes for flavivirus replication. Starting from an in silico docking analysis we identified a pyridobenzothiazole compound, HeE1-2Tyr, able to inhibit West Nile and Dengue RdRps activity in vitro, which proved effective against different flaviviruses in cell culture. Crystallographic data show that HeE1-2Tyr binds between the fingers domain and the priming loop of Dengue virus RdRp (Site 1). Conversely, enzyme kinetics, binding studies and mutational analyses suggest that, during the catalytic cycle and assembly of the RdRp-RNA complex, HeE1-2Tyr might be hosted in a distinct binding site (Site 2)...
October 2016: Antiviral Research
Massimiliano Bissa, Elena Quaglino, Carlo Zanotto, Elena Illiano, Valeria Rolih, Sole Pacchioni, Federica Cavallo, Carlo De Giuli Morghen, Antonia Radaelli
The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required...
October 2016: Antiviral Research
C Joaquín Cáceres, Jenniffer Angulo, Nataly Contreras, Karla Pino, Jorge Vera-Otarola, Marcelo López-Lastra
Replication of the human immunodeficiency virus type 1 (HIV-1) is dependent on eIF5A hypusination. Hypusine is formed post-translationally on the eIF5A precursor by two consecutive enzymatic steps; a reversible reaction involving the enzyme deoxyhypusine synthase (DHS) and an irreversible step involving the enzyme deoxyhypusine hydroxylase (DOHH). In this study we explored the effect of inhibiting DOHH activity and therefore eIF5A hypusination, on HIV-1 gene expression. Results show that the expression of proteins from an HIV-1 molecular clone is reduced when DOHH activity is inhibited by Deferiprone (DFP) or Ciclopirox (CPX)...
October 2016: Antiviral Research
Jialei Sun, Jane Ennis, Jeffrey D Turner, Justin Jang Hann Chu
Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6-day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71...
October 2016: Antiviral Research
Ana Rita de Toledo-Piza, Cristina Adelaide Figueiredo, Maria Isabel de Oliveira, Giuseppina Negri, Gislene Namiyama, Mariana Tonelotto, Karina de Senna Villar, Henrique Krambeck Rofatto, Ronaldo Zucatelli Mendonça
Measles is a viral disease highly contagious spread by respiratory transmission. Although infection can be controlled by vaccination, numerous cases of measles have been registered in many areas of the world, highlighting the need for additional interventions. Terrestrial gastropods exude mucus on their body surface when traveling, to protect the body from mechanical injury, desiccation or contact with harmful substances. The mucus of mollusks has been studied as a source of new natural compounds with diverse biological activities...
October 2016: Antiviral Research
Isolde Schuster, Marc Mertens, Bernd Köllner, Tomáš Korytář, Markus Keller, Bärbel Hammerschmidt, Thomas Müller, Noël Tordo, Philippe Marianneau, Claudia Mroz, Melanie Rissmann, Eileen Stroh, Lisa Dähnert, Felicitas Hammerschmidt, Rainer G Ulrich, Martin H Groschup
Crimean-Congo hemorrhagic fever virus (CCHFV) circulates in many countries of Asia, Africa, and Europe. CCHFV can cause a severe hemorrhagic fever in humans with case-fatality rates of up to 80%. CCHF is considered to be one of the major emerging diseases spreading to and within Europe. Ticks of the genus Hyalomma function as vector as well as natural reservoir of CCHFV. Ticks feed on various domestic animals (e.g. cattle, sheep, goats) and on wildlife (e.g. hares, hedgehogs). Those animal species play an important role in the life cycle of the ticks as well as in amplification of CCHFV...
October 2016: Antiviral Research
Chunlan Liu, Dawei Cai, Lin Zhang, Wei Tang, Ran Yan, Haitao Guo, Xulin Chen
The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication...
October 2016: Antiviral Research
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