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Varun K Phadke, Rachel J Friedman-Moraco, Brian C Quigley, Alton B Farris, J P Norvell
BACKGROUND: Herpesvirus infections often complicate the clinical course of patients with inflammatory bowel disease; however, invasive disease due to herpes simplex virus is distinctly uncommon. METHODS: We present a case of herpes simplex virus colitis and hepatitis, review all the previously published cases of herpes simplex virus colitis, and discuss common clinical features and outcomes. We also discuss the epidemiology, clinical manifestations, diagnosis, and management of herpes simplex virus infections, focusing specifically on patients with inflammatory bowel disease...
October 2016: Medicine (Baltimore)
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
Sawsan Mahmoud, Hao Li, Tamara R McBrayer, Leda Bassit, Sherif F Hammad, Steven J Coats, Franck Amblard, Raymond F Schinazi
A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.
October 19, 2016: Nucleosides, Nucleotides & Nucleic Acids
André Huss, Mathias Buttmann, Isabel Brecht, Andreas Weishaupt, Markus Otto, Hayrettin Tumani
OBJECTIVES: Beside the determination of oligoclonal bands (OCBs) as a diagnostic biomarker in multiple sclerosis (MS), the presence of an intrathecal production of antibodies against the neurotropic viruses measles (M), rubella (R) and Varicella-Zoster (Z), the so called MRZ reaction (MRZR) is an even more specific diagnostic biomarker in MS. METHODS: We compared and validated the determination of the MRZR in 97 cerebrospinal fluid (CSF) and serum sample pairs of a bead-based multiplexing technique and a classical enzyme-linked immunosorbent assay (ELISA)...
October 19, 2016: Expert Review of Molecular Diagnostics
Aleksandar Antanasijevic, Nicholas J Hafeman, Smanla Tundup, Carolyn Kingsley, Rama K Mishra, Lijun Rong, Balaji Manicassamy, Duncan Wardrop, Michael Caffrey
The viral envelope protein hemagglutinin (HA) plays a critical role in influenza entry and thus is an attractive target for novel therapeutics. The small molecule tert-butylhydroquinone (TBHQ) has previously been shown to bind to HA and inhibit HA-mediated entry with low micromolar potency. However, enthusiasm for the use of TBHQ has diminished due to the compound's antioxidant properties. In this work we show that the antioxidant properties of TBHQ are not responsible for the inhibition of HA-mediated entry...
September 9, 2016: ACS Infectious Diseases
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
Matthew L Paff, Scott L Nuismer, Andrew D Ellington, Ian J Molineux, Ryan H May, James J Bull
BACKGROUND: We propose, model, and implement a novel system of population-level intervention against a virus. One context is a treatment against a chronic infection such as HIV. The underlying principle is a form of virus 'wars' in which a benign, transmissible agent is engineered to protect against infection by and spread of a lethal virus. In our specific case, the protective agent consists of two entities, a benign virus and a gene therapy vector mobilized by the benign virus. RESULTS: Numerical analysis of a mathematical model identified parameter ranges in which adequate, population-wide protection is achieved...
2016: Journal of Biological Engineering
Boopathy Ramakrishnan, Karthik Viswanathan, Kannan Tharakaraman, Vlado Dančík, Rahul Raman, Gregory J Babcock, Zachary Shriver, Ram Sasisekharan
Broadly neutralizing monoclonal antibodies (bNAbs) for viral infections, such as HIV, respiratory syncytial virus (RSV), and influenza, are increasingly entering clinical development. For influenza, most neutralizing antibodies target influenza virus hemagglutinin. These bNAbs represent an emerging, promising modality for treatment and prophylaxis of influenza due to their multiple mechanisms of antiviral action and generally safe profile. Preclinical work in other viral diseases, such as dengue, has demonstrated the potential for antibody-based therapies to enhance viral uptake, leading to enhanced viremia and worsening of disease...
October 14, 2016: Trends in Microbiology
Mayuresh Chaudhari, Sonu Sharma, Rajesh Kumar Jha, Ramandeep Singh Ahuja, Sandeep Bansal
Primary varicella infection in an immunocompetent young adult is very rare, but it has a high mortality rate due to serious complications. We report a rare association of varicella pneumonia presenting in acute respiratory distress with mild chest pain, however with electrocardiographic and biochemical markers suggestive of acute ST elevation myocardial infarction. Coronary angiography was done to exclude infarction, serum antibody titers confirmed varicella, acyclovir was started, and ARDS was successfully treated with steroid pulse therapy and mechanical ventilator support...
September 2016: Indian Heart Journal
Satoru Hagiwara, Naoshi Nishida, Tomohiro Watanabe, Toshiharu Sakurai, Hiroshi Ida, Yasunori Minami, Masahiro Takita, Tomohiro Minami, Mina Iwanishi, Hirokazu Chishina, Kazuomi Ueshima, Yoriaki Komeda, Tadaaki Arizumi, Masatoshi Kudo
OBJECTIVE: Treatment for chronic hepatitis C has recently developed in a very rapid manner. In Japan, in September 2014, IFN-free asunaprevir (ASV) and daclatasvir (DCV) became available for combination therapy. We report the treatment outcomes achieved at our hospital using this combination therapy. METHODS: Sustained virological response (SVR) 24 could be evaluated in 120 of 125 patients with chronic liver disease type C who visited our hospital and were treated with ASV/DCV after September 2014, and these patients were analyzed...
2016: Digestive Diseases
Dorota G Piotrowska, Graciela Andrei, Dominique Schols, Robert Snoeck, Magdalena Łysakowska
Cycloadditions of N-substituted C-(diethoxyphosphoryl)nitrones to N-allylated quinazoline-2,4-diones functionalized at N3 with substituted benzoyl or benzyl groups proceeded with moderate to good diastereoselectivities (d.e. 28-68%). The synthesized isoxazolidine phosphonates were assessed for the antiviral activity against a broad range of DNA and RNA viruses. Compounds trans-13c, cis-13c/trans-13c (86:14), cis-15b/trans-15b (87:13) and trans-15d/cis-15d (95:5) exhibited the highest activity toward both TK(+) and TK(-) VZV strains (mean EC50 values in the range of 3...
October 4, 2016: European Journal of Medicinal Chemistry
Andrew V Stachulski, Karl Swift, Mark Cooper, Stephen Reynolds, Daniel Norton, Steven D Slonecker, Jean-François Rossignol
Thiazolides are polypharmacology agents with at least three mechanisms of action against a broad spectrum of parasites, bacteria and viruses. In respiratory viruses they inhibit the replication of orthomyxoviridae and paramyxoviridae at a post-translational level. Nitazoxanide 1a, the prototype thiazolide, was originally developed as an antiparasitic agent and later repurposed for the treatment of viral respiratory infections. The second generation thiazolides following nitazoxanide, such as the 5-chloro analogue RM-5038 2a, are also broad-spectrum antiviral agents as we have reported...
September 26, 2016: European Journal of Medicinal Chemistry
Jovan Nikolic, Ahmet Civas, Zoé Lama, Cécile Lagaudrière-Gesbert, Danielle Blondel
Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection...
October 2016: PLoS Pathogens
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
Yu Mi Seo, Seok Hwang-Bo, Seong Koo Kim, Seung Beom Han, Nack-Gyun Chung, Jin Han Kang
BACKGROUND: Although adenovirus (ADV) infection usually causes self-limiting respiratory disorders in immune competent children; severe and systemic ADV infection in children undergoing chemotherapy for leukemia has been continuously reported. Nevertheless, there has been no consensus on risk factors and treatment strategies for severe ADV infection in children undergoing chemotherapy. CASE SUMMARY: We report a case of a 15-year-old boy with a fatal systemic ADV infection...
October 2016: Medicine (Baltimore)
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)
Chao Liu, Shrinivas G Dumbre, Christophe Pannecouque, Chunsheng Huang, Roger G Ptak, Michael G Murray, Steven De Jonghe, Piet Herdewijn
The synthesis of four l-2'-deoxy-threose nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine, and guanosine has been performed. Especially the adenine containing analogue (PMDTA) was endowed with potent antiviral activity displaying an EC50 of 4.69 μM against HIV-1 and an EC50 value of 0.5 μM against HBV, whereas completely lacking cytotoxicity. The synthesis of a number of phosphonomonoamidate and phosphonobisamidate prodrugs of PMDTA led to a boost in antiviral potency. The most potent congeners were a l-aspartic acid diisoamyl ester phenoxy prodrug and a l-phenylalanine propyl ester phosphonobisamidate prodrug that both display anti-HIV and anti-HBV activities in the low nanomolar range and selectivity indexes of more than 300...
October 17, 2016: Journal of Medicinal Chemistry
Zobair M Younossi, Atsushi Tanaka, Yuichiro Eguchi, Young-Suk Lim, Ming-Lung Yu, Norifumi Kawada, Yock Young Dan, Craig Brooks-Rooney, Francesco Negro, Mario U Mondelli
Between 80 and 115 million people worldwide are chronically infected with hepatitis C virus, with 60-90% of these being undiagnosed. Untreated chronic hepatitis C (CHC) is associated with progressive liver disease, cirrhosis, hepatocellular carcinoma and liver-related mortality. A number of extrahepatic manifestations are also reported in CHC patients, further adding to the burden of the disease. CHC also impacts patients in terms of lower health-related quality of life, higher levels of fatigue and reduced productivity...
October 17, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
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
Kan Xing Wu, Patchara Phuektes, Pankaj Kumar, Germaine Yen Lin Goh, Dimitri Moreau, Vincent Tak Kwong Chow, Frederic Bard, Justin Jang Hann Chu
Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation...
October 17, 2016: Nature Communications
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