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https://www.readbyqxmd.com/read/30108949/conformationally-restricted-benzothienoazepine-respiratory-syncytial-virus-inhibitors-their-synthesis-structural-analysis-and-biological-activities
#1
Euan A F Fordyce, S Fraser Hunt, Damien Crepin, Stuart T Onions, Guillaume F Parra, Chris J Sleigh, John King-Underwood, Harry Finch, John Murray
Atropisomeric drug substances are known to have different biological properties. Compounds containing the N -benzoylbenzazepine motif have been shown to exhibit energetically restricted rotation around the Ar(CO)N axis. Herein we report, for the first time, the synthesis, physical characterisation and anti-viral profiles of a series of C-4 and C-5 methylated thieno-benzazepines. NMR analysis reveals that incorporation of a single additional substituent at either of these loci influences the conformational dynamics of the azepine ring system...
March 1, 2018: MedChemComm
https://www.readbyqxmd.com/read/30107464/hsp90-inhibitor-at-533-blocks-hsv-1-nuclear-egress-and-assembly
#2
Feng Li, Fujun Jin, Yiliang Wang, Danlin Zheng, Junwei Liu, Zhen Zhang, Rongze Wang, Dong Dong, Kai Zheng, Yifei Wang
Heat shock protein 90 (Hsp90) has been identified as an essential host factor for the infection and replication of several viruses, including HSV-1. Recent works have clearly shown that Hsp90 plays a role in the early stages of HSV-1 infection, including nuclear import and DNA replication. However, the role of Hsp90 in the late stages of HSV-1 infection remains unclear. In this study, we found that Hsp90 was up-regulated during late viral infection. Treatment with the Hsp90 inhibitor AT-533 significantly decreased the intracellular and extracellular virus titer, and strongly inhibited nucleocapsid egress from the nucleus...
August 10, 2018: Journal of Biochemistry
https://www.readbyqxmd.com/read/30102858/a-small-molecule-compound-has-anti-influenza-a-virus-activity-by-acting-as-a-pb2-inhibitor
#3
Teng Liu, Miaomiao Liu, Feimin Chen, Fangzhao Chen, Yuanxin Tian, Qi Huang, Shu-Wen Liu, Jie Yang
With regular influenza epidemics and the emergence of drug-resistant virus strains, it is extremely crucial to develop effective and low-toxicity anti-influenza A virus drugs that act on conserved sites of novel targets. Here, we identified a novel anti-influenza compound, 1,3-dihydroxy-6-benzo [c] chromene (D715-2441), from a library of 8,026 small molecule compounds using cell-based influenza A infection assays and explored the underlying mechanisms. Our results revealed that D715-2441 possessed antiviral activities against multiple subtypes of influenza A viruses, including H1N1, H3N2, H5N1, H7N9, the clinical isolate 690 (H3 subtype) and oseltamivir-resistant strains with an NA-H274Y mutation, and suppressed the early steps in the virus replication cycle...
August 13, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30102144/evaluation-of-anticoagulant-agents-for-the-treatment-of-human-metapneumovirus-infection-in-mice
#4
Ba Vuong Lê, Martine Jandrot-Perrus, Christian Couture, Liva Checkmahomed, Marie-Christine Venable, Marie-Ève Hamelin, Guy Boivin
Thrombin has been demonstrated to be involved in several viral diseases including human metapneumovirus (hMPV) infections. We previously showed that immediate administration of thrombin inhibitor argatroban post-infection protected mice against hMPV disease. This current work aims at determining whether warfarin and heparin, two other anticoagulants inhibiting thrombin formation and activities, may also be used for treatment against hMPV in vivo. We found that immediate injections of argatroban, warfarin or heparin after virus challenge protected mice against hMPV infection, as evidenced by decreased or no mortality, less weight loss, reduced viral load and attenuated inflammation...
August 10, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/30101187/combination-of-iap-antagonists-and-tnf-%C3%AE-armed-oncolytic-viruses-induce-tumor-vascular-shutdown-and-tumor-regression
#5
Shawn T Beug, Stephanie J Pichette, Martine St-Jean, Janelle Holbrook, Danielle E Walker, Eric C LaCasse, Robert G Korneluk
Smac mimetic compounds (SMCs) are anti-cancer drugs that antagonize Inhibitor of Apoptosis proteins, which consequently sensitize cancer cells to death in the presence of proinflammatory ligands such as tumor necrosis factor alpha (TNF-α). SMCs synergize with the attenuated oncolytic vesicular stomatitis virus (VSVΔ51) by eliciting an innate immune response, which is dependent on the endogenous production of TNF-α and type I interferon. To improve on this SMC-mediated synergistic response, we generated TNF-α-armed VSVΔ51 to produce elevated levels of this death ligand...
September 28, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/30099206/epstein-barr-virus-shedding-in-multiple-sclerosis-similar-frequencies-of-ebv-in-saliva-across-separate-patient-cohorts
#6
David W Holden, Julian Gold, Christopher H Hawkes, Gavin Giovannoni, John M Saxton, Anouska Carter, Basil Sharrack
BACKGROUND: Epstein Barr Virus (EBV) infection is closely associated with multiple sclerosis (MS), but the relationship between viral load and disease activity is unclear. This study tested the observed levels of salivary EBV in MS, as a first step in investigating this relationship. METHODS: Real-time quantitative PCR (qPCR) was used to measure EBV DNA levels in saliva samples from three separate Multiple Sclerosis (MS) patient cohorts. RESULTS: The qPCR assay was used to delineate EBV shedding, defined here as a reliably detectable level of extracellular EBV DNA in saliva...
July 27, 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/30092360/molecular-property-diagnostic-suite-for-diabetes-mellitus-mpds-dm-an-integrated-web-portal-for-drug-discovery-and-drug-repurposing
#7
Anamika Singh Gaur, Selvaraman Nagamani, Karunakar Tanneeru, Dmitry Druzhilovskiy, Anastassia Rudik, Vladimir Poroikov, G Narahari Sastry
Molecular Property Diagnostic Suite - Diabetes Mellitus (MPDSDM ) is a Galaxy-based, open source disease-specific web portal for diabetes. It consists of three modules namely i) data library ii) data processing and iii) data analysis tools. The data library (target library and literature) module provide extensive and curated information about the genes involved in type 1 and type 2 diabetes onset and progression stage (available at http://www.mpds-diabetes.in). The database also contains information on drug targets, biomarkers, therapeutics and associated genes specific to type 1, and type 2 diabetes...
August 6, 2018: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/30092176/hbv-epidemiology-and-genetic-diversity-in-an-area-of-high-prevalence-of-hepatitis-b-in-southern-brazil
#8
Juliana de Paoli, André Castagna Wortmann, Mirelli Gabardo Klein, Vagner Reinaldo Zingalli Bueno Pereira, Adriana Cirolini, Bibiane Godoy, Nelson Jurandi Rosa Fagundes, Jonas Michel Wolf, Vagner Ricardo Lunge, Daniel Simon
BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem in Brazil. HBV endemicity is usually moderate to low according to geographic regions, and high prevalence of this virus has been reported in people of some specific Brazilian counties, including those with a strong influence of Italian colonization in southern Brazil. Analysis of HBV diversity and identification of the main risk factors to HBV infection are necessary to understand hepatitis B epidemiology in these high prevalence regions in southern Brazil...
August 6, 2018: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/30089693/structural-and-functional-characterization-of-membrane-fusion-inhibitors-with-extremely-potent-activity-against-hiv-1-hiv-2-and-simian-immunodeficiency-virus
#9
Huihui Chong, Yuanmei Zhu, Danwei Yu, Yuxian He
T-20 (enfuvirtide) is the only membrane fusion inhibitor available for treatment of viral infection; however, it has low anti-HIV activity and genetic barrier for drug resistance. We recently reported that T-20 sequence-based lipopeptides possess extremely potent in vitro and in vivo efficacies (Ding et al J Virol, 2017; Chong et al J Virol, 2018). Herein, we focused on characterizing the structure-activity relationships of the T-20 derivatives. First, a novel lipopeptide termed LP-52 was generated with improved target-binding stability and anti-HIV activity...
August 8, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30086449/dissecting-complicated-viral-spreading-of-enterovirus-71-using-in-situ-bioorthogonal-fluorescent-labeling
#10
Hong Pan, Xiangjie Yao, Weihua Chen, Fangfang Wang, Huamei He, Lanlan Liu, Yaqing He, Jinquan Chen, Puzi Jiang, Renli Zhang, Yifan Ma, Lintao Cai
Enterovirus 71 (EV71), the major pathogen of hand-foot-and-mouth disease (HFDM), can cause severe neurological and respiratory manifestations in young children. Viral spread route and tissue tropism are key factors contributing to different pathogenicity of EV71, however it remains a challenge to dynamically visualize EV71 infection in vivo. The present study applies an in situ bioorthogonal fluorescent labeling strategy to track clinically isolated EV71 strains with different pathogenicity in neonatal mice...
August 1, 2018: Biomaterials
https://www.readbyqxmd.com/read/30084057/resistance-detection-and-re-treatment-options-in-hepatitis-c-virus-related-chronic-liver-diseases-after-daa-treatment-failure
#11
REVIEW
Evangelista Sagnelli, Mario Starace, Carmine Minichini, Mariantonietta Pisaturo, Margherita Macera, Caterina Sagnelli, Nicola Coppola
BACKGROUND: Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients. METHODS: The Medline was searched for "HCV infection", "HCV treatment", "Directly acting antivirals","HCV resistance"...
August 6, 2018: Infection
https://www.readbyqxmd.com/read/30083396/induction-of-neutralizing-antibody-response-against-koala-retrovirus-korv-and-reduction-in-viral-load-in-koalas-following-vaccination-with-recombinant-korv-envelope-protein
#12
O Olagoke, D Miller, F Hemmatzadeh, T Stephenson, J Fabijan, P Hutt, S Finch, N Speight, P Timms
Koala retrovirus (KoRV) infects the majority of Australia's koalas ( Phascolarctos cinereus ) and has been linked to several life-threatening diseases such as lymphoma and leukemia, as well as Chlamydia and thus poses a threat to the continued survival of this species. While quarantine and antiretroviral drug treatment are possible control measures, they are impractical, leaving vaccination as the only realistic option. In this study, we examined the effect of a recombinant envelope protein-based anti-KoRV vaccine in two groups of South Australian koalas: KoRV infected or KoRV free...
2018: NPJ Vaccines
https://www.readbyqxmd.com/read/30081947/white-paper-on-microbial-anti-cancer-therapy-and-prevention
#13
Neil S Forbes, Robert S Coffin, Liang Deng, Laura Evgin, Steve Fiering, Matthew Giacalone, Claudia Gravekamp, James L Gulley, Hal Gunn, Robert M Hoffman, Balveen Kaur, Ke Liu, Herbert Kim Lyerly, Ariel E Marciscano, Eddie Moradian, Sheryl Ruppel, Daniel A Saltzman, Peter J Tattersall, Steve Thorne, Richard G Vile, Halle Huihong Zhang, Shibin Zhou, Grant McFadden
In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting ('Microbial Based Cancer Therapy') at the US National Cancer Institute in the summer of 2017. Here, we define 'Microbial Therapy' to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields...
August 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30081913/a-bioreactor-system-for-the-manufacture-of-a-genetically-modified-plasmodium-falciparum-blood-stage-malaria-cell-bank-for-use-in-a-clinical-trial
#14
Rebecca Pawliw, Rebecca Farrow, Silvana Sekuloski, Helen Jennings, Julie Healer, Thuan Phuong, Pri Sathe, Cielo Pasay, Krystal Evans, Alan F Cowman, Louis Schofield, Nanhua Chen, James McCarthy, Katharine Trenholme
BACKGROUND: Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)-compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials. METHODS: Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P...
August 6, 2018: Malaria Journal
https://www.readbyqxmd.com/read/30080294/milk-thistle-silybum-marianum-a-concise-overview-on-its-chemistry-pharmacological-and-nutraceutical-uses-in-liver-diseases
#15
REVIEW
Ludovico Abenavoli, Angelo A Izzo, Natasa Milić, Carla Cicala, Antonello Santini, Raffaele Capasso
Milk thistle (MT; Silybum marianum), a member of the Asteraceae family, is a therapeutic herb with a 2,000-year history of use. MT fruits contain a mixture of flavonolignans collectively known as silymarin, being silybin (also named silibinin) the main component. This article reviews the chemistry of MT, the pharmacokinetics and bioavailability, the pharmacologically relevant actions for liver diseases (e.g., anti-inflammatory, immunomodulating, antifibrotic, antioxidant, and liver-regenerating properties) as well as the clinical potential in patients with alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, drug-induced liver injury, and mushroom poisoning...
August 6, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/30077800/synthesis-and-in-vitro-activities-evaluation-of-arctigenin-derivatives-against-spring-viraemia-of-carp-virus
#16
Wei-Chao Chen, Yang Hu, Lei Liu, Yu-Feng Shen, Gao-Xue Wang, Bin Zhu
Spring viraemia of carp virus (SVCV) is a viral fish pathogen causing high mortality in several carp species and other cultivated fish. However, robust anti-SVCV drugs currently are extremely scarce. For the purpose of seeking out anti-SVCV drugs, here a total of 35 arctigenin derivatives were designed, synthesized and evaluated for their anti-viral activities. By comparing the inhibitory concentration at half-maximal activity (IC50 ) of the 15 screened candidate drugs (max inhibitory response surpassing 90%) in epithelioma papulosum cyprini (EPC) cells infected with SVCV, 2Q and 6 A were chosen for additional validation studies, with an IC50 of 0...
August 2, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/30076863/antiviral-activity-of-silymarin-against-mayaro-virus-and-protective-effect-in-virus-induced-oxidative-stress
#17
Fernanda Caetano Camini, Tales Fernando da Silva, Camila Carla da Silva Caetano, Letícia Trindade Almeida, Ariane Coelho Ferraz, Verônica Maria Alves Vitoreti, Breno de Mello Silva, Silvana de Queiroz Silva, José Carlos de Magalhães, Cintia Lopes de Brito Magalhães
Mayaro virus (MAYV) is a neglected arbovirus belonging to the family Togaviridae. Its infection leads to Mayaro fever, with clinical manifestations such as fever, myalgia, headache, rash, arthralgia, vomiting, and diarrhea. The most prominent complaint from infected person is the long-lasting arthritis/arthralgia. The treatment for Mayaro fever is mainly symptom-based and there are no vaccines or antiviral drugs currently available, thus, natural products with anti-MAYV activity may provide a potential alternative...
August 1, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30074983/immunomodulatory-drug-methotrexate-used-to-treat-patients-with-chronic-inflammatory-rheumatisms-post-chikungunya-does-not-impair-the-synovial-antiviral-and-bone-repair-responses
#18
Yosra Bedoui, Claude Giry, Marie-Christine Jaffar-Bandjee, Jimmy Selambarom, Pascale Guiraud, Philippe Gasque
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms (CIR). Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis post-CHIK but its immunomodulatory activity in the context of viral persistence has been a matter of concerns. We herein used a model of primary human synovial fibroblasts (HSF) and the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic infectious settings in the joints of CHIKV infected patients...
August 3, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/30072974/when-hepatitis-b-virus-meets-interferons
#19
REVIEW
Guangyun Tan, Hongxiao Song, Fengchao Xu, Genhong Cheng
Chronic hepatitis B virus (HBV) infection imposes a severe burden on global public health. Currently, there are no curative therapies for millions of chronic HBV-infected patients (Lok et al., 2017). Interferon (IFN; including pegylated IFN) is an approved anti-HBV drug that not only exerts direct antiviral activity, but also augments immunity against HBV infection. Through a systematic review of the literature, here we summarize and present recent progress in research regarding the interactions between IFN and HBV as well as dissect the antiviral mechanisms of IFN...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30061280/development-and-validation-of-a-phenotypic-high-content-imaging-assay-for-assessing-the-antiviral-activity-of-small-molecule-inhibitors-targeting-the-zika-virus
#20
Jean A Bernatchez, Zunhua Yang, Michael Coste, Jerry Li, Sungjun Beck, Yan Liu, Alex E Clark, Zhe Zhu, Lucas A Luna, Christal D Sohl, Byron W Purse, Rongshi Li, Jair L Siqueira-Neto
Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barré syndrome. There are currently no drugs available to treat infection, and accordingly there is an unmet medical need for discovery of new therapies. High-throughput drug screening efforts focusing on indirect readouts of cell viability are prone to a higher frequency of false positives in cases where the virus is viable in the cell but the cytopathic effect is reduced or delayed. Here, we describe a fast and label-free phenotypic high-content imaging assay used to detect cells affected by the viral-induced cytopathic effect (CPE) using automated imaging and analysis...
July 30, 2018: Antimicrobial Agents and Chemotherapy
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