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ANTIVIRAL DRUGS

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https://www.readbyqxmd.com/read/28645740/safety-of-the-2d-3d-direct-acting-antiviral-regimen-in-hcv-induced-child-pugh-a-cirrhosis-a-pooled-analysis
#1
Fred Poordad, David R Nelson, Jordan J Feld, Michael W Fried, Heiner Wedemeyer, Lois Larsen, Daniel E Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R Foster
BACKGROUND & AIMS: Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r ± DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis. METHODS: Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r ± ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r + DSV ± RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment...
June 20, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28644739/treatment-of-hepatitis-c-with-new-fixed-dose-combinations
#2
Vicente Soriano
The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc...
June 23, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28640902/hepatitis-b-virus-reactivation-and-antiviral-prophylaxis-during-lung-cancer-chemotherapy-a-systematic-review-and-meta-analysis
#3
Yu-Tuan Wu, Xin Li, Zi-Li Liu, Zhou Xu, Wei Dai, Ke Zhang, Jiu-Song Wu, Bilal Arshad, Kai-Nan Wu, Ling-Quan Kong
BACKGROUND: Antiviral drugs have been recommended as prophylaxis for the reactivation of hepatitis B virus (HBV) infection in cancer patients undergoing chemotherapy. However, screening and antiviral prophylaxis for lung cancer remain controversial because of insufficient evidence. PURPOSE: In this study, we investigate the absolute risk for HBV reactivation and the prophylactic effects of antiviral drugs in hepatitis B surface antigen (HBsAg)-positive lung cancer patients during chemotherapy...
2017: PloS One
https://www.readbyqxmd.com/read/28640812/challenges-in-preparing-and-implementing-a-clinical-trial-at-field-level-in-an-ebola-emergency-a-case-study-in-guinea-west-africa
#4
Sara Carazo Perez, Elin Folkesson, Xavier Anglaret, Abdoul-Habib Beavogui, Emmanuel Berbain, Alseny-Modet Camara, Evelyn Depoortere, Annabelle Lefevre, Piet Maes, Kristian Nødtvedt Malme, Jean-Marie Denis Malvy, Sien Ombelet, Geertrui Poelaert, Daouda Sissoko, Alexis Tounkara, Pierre Trbovic, Pascal Piguet, Annick Antierens
During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved...
June 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28640212/synthesis-and-in-vitro-anti-influenza-virus-evaluation-of-novel-sialic-acid-c-5-and-c-9-pentacyclic-triterpene-derivatives
#5
Xu Han, Long-Long Si, Yong-Ying Shi, Zi-Bo Fan, Shou-Xin Wang, Zhen-Yu Tian, Man Li, Jia-Qi Sun, Ping-Xuan Jiao, Fu-Xiang Ran, Yong-Min Zhang, De-Min Zhou, Su-Long Xiao
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates...
June 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28639277/serum-derived-transfer-factor-stimulates-the-innate-immune-system-to-improve-survival-traits-in-high-risk-pathogen-scenarios
#6
Bridget V Willeford, Trudy Shapiro-Dunlap, Kenneth O Willeford
Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0...
June 22, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28638862/raw-rehmannia-radix-polysaccharide-can-effectively-release-peroxidative-injury-induced-by-duck-hepatitis-a-virus
#7
Meiyun Song, Yun Chen, Hongxu Du, Shuaibing Zhang, Yixuan Wang, Ling Zeng, Jingjing Yang, Jintong Shi, Yi Wu, Deyun Wang, Yuanliang Hu, Jiaguo Liu
BACKGROUND: Duck viral hepatitis (DVH), caused by duck hepatitis A virus (DHAV), is a fatal contagious infectious disease which spreads rapidly with high morbidity and high mortality, and there is no effective clinical drug against DVH. MATERIALS AND METHODS: Raw Rehmannia Radix Polysaccharide (RRRP), Lycii Fructus polysaccharides and Astragalus Radix polysaccharides were experimented in vitro and in vivo. Mortality rate, livers change, liver lesion scoring, peroxidative injury evaluation indexes in vitro and in vivo, and hepatic injury evaluation indexes of optimal one were detected and observed in this experiment...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28638769/deeper-insight-into-the-six-step-domino-reaction-of-aldehydes-with-malononitrile-and-evaluation-of-antiviral-and-antimalarial-activities-of-the-obtained-bicyclic-products
#8
Christina M Bock, Gangajji Parameshwarappa, Simon Bönisch, Walter Bauer, Corina Hutterer, Maria Leidenberger, Oliver Friedrich, Manfred Marschall, Barbara Kappes, Andreas Görling, Svetlana B Tsogoeva
The straightforward and efficient synthesis of complex aza- and carbobicyclic compounds, which are of importance for medicinal chemistry, is a challenge for modern chemical methodology. An unprecedented metal-free six-step domino reaction of aldehydes with malononitrile was presented in our previous study to provide, in a single operation, these bicyclic nitrogen-containing molecules. Presented here is a deeper investigation of this atom-economical domino process by extending the scope of aldehydes, performing post-modifications of domino products, applying bifunctional organocatalysts and comprehensive NMR studies of selected domino products...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28638096/identification-of-a-flavonoid-isolated-from-plum-prunus-domestica-as-a-potent-inhibitor-of-hepatitis-c-virus-entry
#9
Mihika Bose, Mohini Kamra, Ranajoy Mullick, Santanu Bhattacharya, Saumitra Das, Anjali A Karande
Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases that often requires liver transplantation. The standard therapies are limited by severe side effects, resistance development, high expense and in a substantial proportion of cases, fail to clear the infection which bespeak the need for development of well-tolerated antivirals. Since most of the drug development strategies target the replication stage of viral lifecycle, the identification of entry inhibitors might be crucial especially in case of liver-transplant recipients...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637759/role-of-jnk-pathway-in-varicella-zoster-virus-lytic-infection-and-reactivation
#10
Sravya Kurapati, Tomohiko Sadaoka, Labchan Rajbhandari, Balaji Jagdish, Priya Shukla, Yong Jun Kim, Gabsang Lee, Jeffrey I Cohen, Arun Venkatesan
Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen activated protein kinases (MAPKs) have been shown to play a role in VZV infection of non-neuronal cells, with distinct consequences on infectivity in differing cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28637387/immunopathology-of-chikungunya-virus-infection-lessons-learned-from-patients-and-animal-models
#11
Lisa F P Ng
Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes acute and chronic arthritis. The virus reemerged in the Indian Ocean islands in 2005-2006 and is responsible for outbreaks in the Caribbean islands and the Americas since late 2013. Despite the wealth of research over the past 10 years, there are no commercially available antiviral drugs or vaccines. Treatment usually involves analgesics, anti-inflammatory drugs, and supportive care. Most studies have been focused on understanding the pathogenesis of CHIKV infection through clinical observation and with animal models...
June 21, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28636622/inhibition-of-hepatitis-b-viral-entry-by-nucleic-acid-polymers-in-heparg-cells-and-primary-human-hepatocytes
#12
Clément Guillot, Nora Martel, Françoise Berby, Isabelle Bordes, Olivier Hantz, Matthieu Blanchet, Camille Sureau, Andrew Vaillant, Isabelle Chemin
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure...
2017: PloS One
https://www.readbyqxmd.com/read/28634494/antiviral-activity-of-fridericia-formosa-bureau-l-g-lohmann-bignoniaceae-extracts-and-constituents
#13
Geraldo Célio Brandão, Erna G Kroon, José D Souza Filho, Alaíde Braga Oliveira
A phytochemical study of Fridericia formosa (Bignoniaceae) ethanol extracts of leaves, stems, and fruits was guided by in vitro assays against vaccinia virus Western Reserve (VACV-WR), human herpes virus 1 (HSV-1), murine encephalomyocarditis virus (EMCV), and dengue virus type 2 (DENV-2) by the MTT method. All the ethanol extracts were active against DENV-2, HSV-1, and VACV-WR with best results for the fruits extract against DENV-2 (SI > 38.2). For VACV-WR and HSV-1, EC50 values > 200 μg mL(-1) were determined, while no inhibition of the cytopathic effect was observed with EMCV...
2017: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28634358/hiv-1-gp41-targeting-fusion-inhibitory-peptides-enhance-the-gp120-targeting-protein-mediated-inactivation-of-hiv-1-virions
#14
Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang
Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT)...
June 21, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28634131/cost-effectiveness-of-pre-versus-post-liver-transplant-hepatitis-c-treatment-with-direct-acting-antivirals
#15
Sumeyye Samur, Brian Kues, Turgay Ayer, Mark S Roberts, Fasiha Kanwal, Chin Hur, Drew Michael S Donnell, Raymond T Chung, Jagpreet Chhatwal
BACKGROUND & AIMS: Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment offer new hope to both pre- and post-liver transplant (LT) patients. However, whether to treat HCV patients pre- versus post-LT is not clear, as treatment can improve liver function but could reduce the chance of receiving a LT while on the waiting list. Our objective was to evaluate the cost-effectiveness of pre-LT versus post-LT HCV treatment with oral DAAs in decompensated cirrhotic patients on the LT waiting list...
June 17, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28633989/efficacy-and-cytotoxicity-in-cell-culture-of-novel-%C3%AE-hydroxytropolone-inhibitors-of-hepatitis-b-virus-ribonuclease-h
#16
Elena Lomonosova, Jil Daw, Aswin K Garimallaprabhakaran, Nana B Agyemang, Yashkumar Ashani, Ryan P Murelli, John E Tavis
Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct-acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that α-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication. Subsequently, we found that our biochemical RNaseH assay underreports efficacy of the α-hydroxytropolones against HBV replication. Therefore, we conducted a structure-activity analysis of 59 troponoids against HBV replication in cell culture...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633752/rituximab-administration-in-a-patient-with-pemphigus-vulgaris-following-reactivation-of-occult-hepatitis-b-virus-infection
#17
Soheil Tavakolpour, Tahereh Soori, Pedram Noormohammadpour, Kamran Balighi, Hamidreza Mahmoudi, Maryam Daneshpazhooh
Immunosuppressive drugs are the milestone of treatment of autoimmune diseases, but they can lead to serious complications, including hepatitis B virus reactivation in HBV carriers as well as in patients with occult HBV infection (OBI). A 36-year-old man with OBI was diagnosed with pemphigus vulgaris. He was prescribed prednisolone and his hepatitis B surface antigen turned positive. Viral replication was successfully controlled by lamivudine and adefovir. Mycophenolate mofetil and intravenous immunoglobulin  were not effective in controlling the pemphigus vulgaris...
June 20, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28632788/high-throughput-identification-and-rational-design-of-synergistic-small-molecule-pairs-for-combating-and-bypassing-antibiotic-resistance
#18
Morgan A Wambaugh, Viplendra P S Shakya, Adam J Lewis, Matthew A Mulvey, Jessica C S Brown
Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28632758/safety-and-tolerability-of-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate-in-a-real-life-setting-data-from-surveillance-cohort-long-term-toxicity-antiretrovirals-antivirals-scolta-project
#19
Nicola Squillace, Elena Ricci, Tiziana Quirino, Andrea Gori, Alessandra Bandera, Laura Carenzi, Giuseppe Vittorio De Socio, Giancarlo Orofino, Canio Martinelli, Giordano Madeddu, Stefano Rusconi, Paolo Maggi, Benedetto Maurizio Celesia, Laura Cordier, Francesca Vichi, Leonardo Calza, Katia Falasca, Antonio Di Biagio, Giovanni Francesco Pellicanò, Paolo Bonfanti
OBJECTIVES: The study aim was to evaluate the impact on Liver and Kidney toxicity of the single tablet regimen Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF) on Antiretroviral Therapy (ART) experienced or naïve patients. METHODS: Patients initiating EVG/COBI/FTC/TDF were enrolled in the SCOLTA project, a multicenter observational study reporting grade 3-4 Adverse Events in subjects beginning new antiretroviral drug regimens...
2017: PloS One
https://www.readbyqxmd.com/read/28630251/valnoctamide-inhibits-cytomegalovirus-infection-in-developing-brain-and-attenuates-neurobehavioral-dysfunctions-and-brain-abnormalities
#20
Sara Ornaghi, Lawrence S Hsieh, Angélique Bordey, Patrizia Vergani, Michael J Paidas, Anthony N van den Pol
Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antivirals, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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