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ANTIVIRAL DRUGS

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https://www.readbyqxmd.com/read/28426799/cell-cycle-profiling-by-image-and-flow-cytometry-the-optimised-protocol-for-the-detection-of-replicational-activity-using-5-bromo-2-deoxyuridine-low-concentration-of-hydrochloric-acid-and-exonuclease-iii
#1
Anna Ligasová, Petr Konečný, Ivo Frydrych, Karel Koberna
The approach for the detection of replicational activity in cells using 5-bromo-2'-deoxyuridine, a low concentration of hydrochloric acid and exonuclease III is presented in the study. The described method was optimised with the aim to provide a fast and robust tool for the detection of DNA synthesis with minimal impact on the cellular structures using image and flow cytometry. The approach is based on the introduction of breaks into the DNA by the low concentration of hydrochloric acid followed by the subsequent enzymatic extension of these breaks using exonuclease III...
2017: PloS One
https://www.readbyqxmd.com/read/28426720/a-new-model-mimicking-persistent-hbv-e-antigen-negative-infection-using-covalently-closed-circular-dna-in-immunocompetent-mice
#2
Lei Wang, Min Cao, Qing Lu Wei, Zhong Hua Zhao, Qin Xiang, Hui Juan Wang, Hua Tang Zhang, Guo Qi Lai
Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem. HBV e antigen (HBeAg)-negative strains have become prevalent. Previously, no animal model mimicked the clinical course of HBeAg-negative HBV infection. To establish an HBeAg-negative HBV infection model, the 3.2-kb full-length genome of HBeAg-negative HBV was cloned from a clinical sample and then circularized to form covalently closed circular (cccDNA). The resulting cccDNA was introduced into the liver of C57BL/6J mice through hydrodynamic injection...
2017: PloS One
https://www.readbyqxmd.com/read/28426220/fluorescent-neuraminidase-assay-based-on-supramolecular-dye-capture-after-enzymatic-cleavage
#3
Wenqi Liu, César F A Gómez-Durán, Bradley D Smith
A conceptually new type of enzymatic cleavage assay is reported that utilizes in-situ supramolecular capture of the fluorescent product. A squaraine-derived substrate with large blocking groups at each end of its structure cannot be threaded by a tetralactam macrocycle until the blocking groups are removed by enzyme cleavage. A prototype design responds to viral neuraminidase, an indicator of influenza infection, and also measures susceptibility of the sample to neuraminidase inhibitor drugs. The substrate structure incorporates three key features; (a) a bis(4-amino-3-hydroxyphenyl)squaraine core with bright deep-red fluorescence and excellent photostability, (b) an N-methyl group at each end of the squaraine core that ensures fast macrocycle threading kinetics, and (c) sialic acid blocking groups that prevent macrocycle threading until they are removed by viral neuraminidase...
April 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28425406/curing-chronic-hepatitis-c-a-cost-comparison-of-the-combination-simeprevir-plus-sofosbuvir-vs-protease-inhibitor-based-triple-therapy
#4
Jacob A Langness, David Tabano, Amanda Wieland, Sarah Tise, Lindsay Pratt, Lauren Ayres Harrington, Sonia Lin, Vahram Ghuschcyan, Kavita V Nair, Gregory T Everson
INTRODUCTION: Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. MATERIAL AND METHODS: Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28424287/protective-efficacy-of-formaldehyde-inactivated-whole-virus-vaccine-and-antivirals-in-a-murine-model-of-coxsackievirus-a10-infection
#5
Zhenjie Zhang, Zhaopeng Dong, Juan Li, Michael J Carr, Dongming Zhuang, Jianxing Wang, Yawei Zhang, Shujun Ding, Yigang Tong, Dong Li, Weifeng Shi
Coxsackievirus A10 (CVA10) is one of the major pathogens associated with hand, foot and mouth disease (HFMD). CVA10 infection can cause herpangina and viral pneumonia, which can be complicated by severe neurological sequelae. Morbidity and mortality of CVA10-associated HFMD has been increasing in recent years, particularly in the pan-Pacific region. There are limited studies however on the pathogenesis and immunology of CVA10-associated HFMD infections, and few antiviral drugs or vaccines have been reported...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28423338/an-amphibian-host-defense-peptide-is-virucidal-for-human-h1-hemagglutinin-bearing-influenza-viruses
#6
David J Holthausen, Song Hee Lee, Vineeth Tv Kumar, Nicole M Bouvier, Florian Krammer, Ali H Ellebedy, Jens Wrammert, Anice C Lowen, Sanil George, Madhavan Radhakrishna Pillai, Joshy Jacob
Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28423309/the-natural-product-cavinafungin-selectively-interferes-with-zika-and-dengue-virus-replication-by-inhibition-of-the-host-signal-peptidase
#7
David Estoppey, Chia Min Lee, Marco Janoschke, Boon Heng Lee, Kah Fei Wan, Hongping Dong, Philippe Mathys, Ireos Filipuzzi, Tim Schuhmann, Ralph Riedl, Thomas Aust, Olaf Galuba, Gregory McAllister, Carsten Russ, Martin Spiess, Tewis Bouwmeester, Ghislain M C Bonamy, Dominic Hoepfner
Flavivirus infections by Zika and dengue virus impose a significant global healthcare threat with no US Food and Drug Administration (FDA)-approved vaccination or specific antiviral treatment available. Here, we present the discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin is a potent and selectively active compound against Zika and all four dengue virus serotypes. Unbiased, genome-wide genomic profiling in human cells using a novel CRISPR/Cas9 protocol identified the endoplasmic-reticulum-localized signal peptidase as the efficacy target of cavinafungin...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422294/antiviral-activity-of-exopolysaccharides-from-arthrospira-platensis-against-koi-herpesvirus
#8
M Reichert, S M Bergmann, J Hwang, R Buchholz, C Lindenberger
Although koi herpesvirus (KHV) has a history of causing severe economic losses in common carp and koi farms, there are still no treatments available on the market. Thus, the aim of this study was to test exopolysaccharides (EPS) for its antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in common carp brain cells. These substances can be easily extracted from extracellular algae supernatant and were identified as groups of sulphated polysaccharides. In order to reach this aim, Arthrospira platensis, which is well known for its antiviral activity of intra- and extracellular compounds towards mammalian herpesviruses, was investigated as standard organism and compared to commercial antiviral drug, ganciclovir, which inhibits the viral DNA polymerization...
April 19, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28421048/functional-information-stored-in-the-conserved-structural-rna-domains-of-flavivirus-genomes
#9
REVIEW
Alba Fernández-Sanlés, Pablo Ríos-Marco, Cristina Romero-López, Alfredo Berzal-Herranz
The genus Flavivirus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses. Like other RNA viruses, flaviviruses have a compact RNA genome that efficiently stores all the information required for the completion of the infectious cycle...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419938/direct-acting-antivirals-the-endgame-for-hepatitis-c
#10
REVIEW
Roberta D'Ambrosio, Elisabetta Degasperi, Massimo Colombo, Alessio Aghemo
Directly-acting antivirals (DAA) have finally allowed all patients to be potentially cured from chronic hepatitis C (HCV) infection. All-oral, Interferon (IFN)-free regimens are based upon the combination of molecules targeting different sites of the HCV replication process. Three classes of DAA exist: protease inhibitors (anti-NS3/4A), RNA-dependent polymerase inhibitors (anti-NS5B) and anti-NS5A inhibitors, which are characterized by different antiviral potency and barrier to resistance and therefore are usually combined in different treatment schedules...
April 15, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28418652/design-and-development-of-highly-potent-hiv-1-protease-inhibitors-with-a-crown-like-oxotricyclic-core-as-the-p2-ligand-to-combat-multidrug-resistant-hiv-variants
#11
Arun K Ghosh, Kalapala Venkateswara Rao, Prasanth R Nyalapatla, Heather L Osswald, Cuthbert D Martyr, Manabu Aoki, Hironori Hayashi, Johnson Agniswamy, Yuan-Fang Wang, Haydar Bulut, Debananda Das, Irene T Weber, Hiroaki Mitsuya
Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1 protease inhibitors are reported. Inhibitor 5 displayed superior antiviral activity and drug-resistance profiles. In fact, this inhibitor showed several orders of magnitude improved antiviral activity over the FDA approved drug darunavir. This inhibitor incorporates an unprecedented 6-5-5 ring-fused crown-like tetrahydropyranofuran as the P2 ligand and an aminobenzothiazole as the P2' ligand with the (R)-hydroxyethylsulfonamide isostere...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418295/phenotypic-and-genotypic-shifts-in-hepatitis-b-virus-in-treatment-naive-patients-taiwan-2008-2012
#12
Chau-Ting Yeh, Kung-Hao Liang, Ming-Ling Chang, Chao-Wei Hsu, Yi-Cheng Chen, Chih-Lang Lin, Wey-Ran Lin, Ming-Wei Lai
We examined the characteristic changes of hepatitis B virus (HBV) in antiviral drug treatment-naive patients referred for pretreatment evaluation in Taiwan during 2008-2012. Over time, we observed substantial decreases in the prevalence of HBV e antigen (HBeAg) and increasing prevalence of the precore G1899A mutation and HBV-DNA levels in HBeAg-positive patients.
May 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28418242/slow-but-steady-wins-the-race-dissimilarities-among-new-dual-inhibitors-of-the-wild-type-and-the-v27a-mutant-m2-channels-of-influenza-a-virus
#13
Marta Barniol-Xicota, Sabrina Gazzarrini, Eva Torres, Yanmei Hu, Jun Wang, Lieve Naesens, Anna Moroni, Santiago Vazquez
New insights on the amantadine resistance mechanism of the V27A mutant were obtained through the study of novel, easily accessible 4-(1- and 2-adamantyl)piperidines, identified as dual binders of the wild-type and V27A mutant M2 channels of influenza A virus. Their antiviral activity and channel blocking ability were determined using cell-based assays and two-electrode voltage clamp (TEVC) technique on M2 channels, respectively. In addition, electrophysiology experiments revealed two interesting findings: i) these inhibitors display a different behaviour against the wild-type versus V27A mutant A/M2 channels and, ii) the compounds display antiviral activity when have kd equal or smaller than 10-6 while do not exhibit antiviral activity when kd is 10-5 or higher although may show blocking activity in the TEV assay...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28417913/comparative-study-on-the-antivirus-activity-of-shuang-huang-lian-injectable-powder-and-its-bioactive-compound-mixture-against-human-adenovirus-iii-in-vitro
#14
Qinhai Ma, Dedong Liang, Shuai Song, Qintian Yu, Chunyu Shi, Xuefeng Xing, Jia-Bo Luo
Shuang-Huang-Lian injectable powder (SHL)-a classical purified herbal preparation extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense-has been used against human adenovirus III (HAdV₃) for many years. The combination herb and its major bioactive compounds, including chlorogenic acid, baicalin, and forsythia glycosides A, are effective inhibitors of the virus. However, no comprehensive studies are available on the antiviral effects of SHL against HAdV₃. Moreover, it remains unclear whether the mixture of chlorogenic acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity compared with SHL...
April 12, 2017: Viruses
https://www.readbyqxmd.com/read/28416549/antiviral-activity-and-resistance-analysis-of-ns3-4a-protease-inhibitor-grazoprevir-and-ns5a-inhibitor-elbasvir-in-hepatitis-c-virus-gt4-replicons
#15
Ernest Asante-Appiah, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Robert Chase, David Nickle, Ping Qiu, Anita Howe, Frederick C Lahser
Although genotype (GT) 4-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents: grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor, in GT4 replicons prior to clinical studies in this genotype...
April 17, 2017: Antimicrobial Agents and Chemotherapy
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
#16
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/28412701/association-between-medications-and-herpes-zoster-in-japanese-patients-with-rheumatoid-arthritis-a-5-year-prospective-cohort-study
#17
Sayoko Harada, Ryoko Sakai, Fumio Hirano, Nobuyuki Miyasaka, Masayoshi Harigai
OBJECTIVE: To investigate the association between medications and herpes zoster (HZ) in patients with rheumatoid arthritis (RA) given biological disease-modifying antirheumatic drugs (bDMARD) or conventional synthetic DMARD in the clinical setting during 5 years using the Registry of Japanese Rheumatoid Arthritis Patients on Biologics for Longterm Safety (REAL) database. METHODS: We calculated the crude incidence rate (IR) of HZ treated with systemic antiviral medications in 1987 patients from the REAL database...
April 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28412273/efficient-inhibition-of-influenza-a-viral-replication-in-cells-by-deoxyribozymes-delivered-by-nanocomposites
#18
Marina Repkova, Asya Levina, Boris Chelobanov, Zinfer Ismagilov, Natalia Shatskaya, Sergei Baiborodin, Ekaterina Filippova, Natalia Mazurkova, Valentina Zarytova
Nucleic-acid-based drugs are a promising class of novel therapeutics; however, their use in medicine is widely limited because of insufficient delivery into cells. This article proposes a new delivery strategy of nucleic acid fragments into cells as components of TiO2-based nanocomposites. For the first time, unmodified Dz molecules were non-covalently immobilized on TiO2 nanoparticles precovered with polylysine (TiO2•PL) with the formation of (TiO2•PL)•Dz nanocomposites. DNAzymes in the proposed nanocomposites were shown to retain their ability to cleave the RNA target in a cell-free system with the same selectivity as unbound Dz molecules...
April 12, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28412182/characterization-of-three-small-molecule-inhibitors-of-enterovirus-71-identified-from-screening-of-a-library-of-natural-products
#19
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/28411509/direct-acting-antivirals-and-host-targeting-strategies-to-combat-enterovirus-infections
#20
REVIEW
Lisa Bauer, Heyrhyoung Lyoo, Hilde M van der Schaar, Jeroen Rpm Strating, Frank Jm van Kuppeveld
Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues...
April 12, 2017: Current Opinion in Virology
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