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Nahid Shahabadi, Mehdi Pourfoulad, Neda Hosseinpour Moghadam
DNA-binding properties of an antiviral drug, valganciclovir (valcyte) was studied by using emission, absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, and computational studies. The drug bound to calf thymus DNA (ct-DNA) in a groove-binding mode. The calculated binding constant of UV-vis, Ka, is comparable to groove-binding drugs. Competitive fluorimetric studies with Hoechst 33258 showed that valcyte could displace the DNA-bound Hoechst 33258. The drug could not displace intercalated methylene blue from DNA double helix...
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
Emma Hathorn, Ahmed M Elsharkawy
Genotype 4 chronic hepatitis C (G4 HCV) accounts for 13% of worldwide HCV infections; with 10 million people infected with the virus across the world. Up to the end of 2013, the only treatment option for G4 HCV was treatment with pegylated interferon and ribavirin for 24-48 weeks. Since late 2013, treatment of G4 HCV has been transformed by the licensing of many directly acting antiviral agents (DAA). It is an exciting time to be involved in the management of HCV generally and G4 particularly. Interferon-free DAA regimens are now a reality for G4 HCV...
2016: BMJ Open Gastroenterology
Laurent Alric, Caroline Besson, Nathanael Lapidus, Juliette Jeannel, Jean-Marie Michot, Patrice Cacoub, Danielle Canioni, Stanislas Pol, Frédéric Davi, Pascaline Rabiega, Loic Ysebaert, Delphine Bonnet, Olivier Hermine
: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL...
2016: PloS One
Zhangmin Tan, Yuzhu Yin, Jin Zhou, Lingling Wu, Chengfang Xu, Hongying Hou
This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination...
October 2016: Medicine (Baltimore)
Hinojal Zazo, Clara I Colino, Klaudia T Warzecha, Mareike Hoss, Uwe Gbureck, Christian Trautwein, Frank Tacke, José M Lanao, Matthias Bartneck
The human immunodeficiency virus (HIV) continues to be a global pandemic and there is an urgent need for innovative treatment. Immune cells represent a major target of virus infection, but are also therapeutic targets. Currently, no antiretroviral therapy targets macrophages, which function as portal of entry and as major long-term deposit of HIV. It has been shown before that human macrophages efficiently internalize gold nanoparticles, a fact which might be used to target them with drug-nanoparticle conjugates...
October 17, 2016: Macromolecular Bioscience
Yong-Qiang Deng, Na-Na Zhang, Chun-Feng Li, Min Tian, Jia-Nan Hao, Xu-Ping Xie, Pei-Yong Shi, Cheng-Feng Qin
The ongoing Zika virus (ZIKV) outbreaks have raised global concerns due to its unexpected clinical manifestations. Antiviral development is of high priority in response to the ZIKV emergency. In this study, we report that an adenosine analog NITD008 has potent in vitro and in vivo antiviral activity against ZIKV. The compound can effectively inhibit the historical and contemporary ZIKV strains in cultures as well as significantly reduce viremia and prevent mortality in A129 mice. Our results have demonstrated that NITD008 is potent inhibitor of ZIKV and can be used as reference inhibitor for future ZIKV antiviral drug screen and discovery...
October 2016: Open Forum Infectious Diseases
Sean Ekins, John Liebler, Bruno J Neves, Warren G Lewis, Megan Coffee, Rachelle Bienstock, Christopher Southan, Carolina H Andrade
The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo...
2016: F1000Research
Christoph Priesner, Ruth Esser, Sabine Tischer, Michael Marburger, Krasimira Aleksandrova, Britta Maecker-Kolhoff, Hans-Gert Heuft, Lilia Goudeva, Rainer Blasczyk, Lubomir Arseniev, Ulrike Köhl, Britta Eiz-Vesper, Stephan Klöß
BACKGROUND AND AIMS: The infusion of enriched CMV-specific donor T-cells appears to be a suitable alternative for the treatment of drug-resistant CMV reactivation or de novo infection after both solid organ and hematopoietic stem cell transplantation. Antiviral lymphocytes can be selected from apheresis products using the CliniMACS Cytokine-Capture-System(®) either with the well-established CliniMACS(®) Plus (Plus) device or with its more versatile successor CliniMACS Prodigy(®) (Prodigy)...
2016: Frontiers in Immunology
Sern Wei Yeoh
Direct acting antiviral (DAA) regimens containing ritonavir have been developed to treat hepatitis C, with fewer side effects than that by interferon-based regimens. However prescribers must be aware of drug-drug interactions. There are multiple reports of iatrogenic Cushing syndrome (CS) caused by ritonavir, when used to treat human immunodeficiency virus, increasing the bioavailability of exogenous steroids by inhibiting cytochrome p450 enzymes in the liver and gut wall and thus reducing steroid metabolism...
September 2016: Journal of Clinical and Experimental Hepatology
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND AND AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 13, 2016: Journal of Hepatology
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
Marianne Uteng, Andreas Mahl, Nicolau Beckmann, Alessandro Piaia, David Ledieu, Valerie Dubost, Elaine Tritto, Armin Wolf, Pierre Moulin, Li Li, Salah-Dine Chibout, Francois Pognan
The aim of this study was to determine the relative safety of four antiviral drugs (telbivudine, tenofovir, adefovir, entecavir) against hepatitis B virus with respect to kidney function and toxicity in male Spraque-Dawley rats. The antiviral drugs were administered once daily for four weeks by oral gavage at about 10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology and electron microscopic examination...
October 13, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
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
L Benítez-Gutiérrez, C de Mendoza, I Baños, A Duca, A Arias, A Treviño, S Requena, M J Citores, V Cuervas-Mons
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015...
September 2016: Transplantation Proceedings
Dongwei Kang, Heng Zhang, Zhongxia Zhou, Boshi Huang, Lieve Naesens, Peng Zhan, Xinyong Liu
A series of 1,2,3-triazolyl 3-hydroxy-quinazoline-2,4(1H,3H)-diones was constructed utilizing Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) method. The biological significance of the novel synthesized quinazolines was highlighted by evaluating them in vitro for antiviral activity, wherein several compounds exhibited excellent activity specifically against vaccinia and adenovirus. Especially, 24b11 displayed the most potent inhibitory activity against vaccinia with an EC50 value of 1.7μM, which was 15 fold than that of the reference drug Cidofovir (EC50=25μM)...
September 29, 2016: Bioorganic & Medicinal Chemistry Letters
Perica Davitkov, Apoorva Krishna Chandar, Amy Hirsch, Anita Compan, Marina G Silveira, Donald D Anthony, Suzanne Smith, Clare Gideon, Robert A Bonomo, Yngve Falck-Ytter
BACKGROUND: Clinicians often face dilemmas with decisions related to formulary choices when two similar drugs are simultaneously available in the market. We studied the comparative safety, effectiveness, and treatment costs of the two first generation direct-acting antiviral agents (DAA), boceprevir and telaprevir as uncertainty existed regarding the drug of choice between these two seemingly equally Hepatitis-C treatment options. METHODS: We randomly assigned 50 patients in an open-label, pragmatic randomized controlled trial (RCT) at a VA Medical Center to either boceprevir or telaprevir in combination with peginterferon and ribavirin, stratified by the presence of cirrhosis and prior treatment experience...
2016: PloS One
Zobair M Younossi, Haesuk Park, Douglas Dieterich, Sammy Saab, Aijaz Ahmed, Stuart C Gordon
BACKGROUND: New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM: The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN: A decision-analytic Markov model...
October 2016: Medicine (Baltimore)
Pratyush Kumar Das, Laura Puusepp, Finny S Varghese, Age Utt, Tero Ahola, Dzmitry G Kananovich, Margus Lopp, Andres Merits, Mati Karelson
Chikungunya virus (CHIKV, genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Joana Rocha-Pereira, Jana Van Dycke, Johan Neyts
Human noroviruses are the leading cause of foodborne illness causing both acute and chronic gastroenteritis. In recent years, a number of vaccine candidates entered (pre-) clinical development and the first efforts to develop antiviral therapy have been made. We here discuss aspects of norovirus genetic evolution, persistence in immunocompromised patients as well as the risk and potential consequences of resistance development toward future antiviral drugs.
October 10, 2016: Current Opinion in Virology
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