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ANTIVIRAL DRUGS

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https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#1
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28087313/an-m2-v27a-channel-blocker-demonstrates-potent-in-vitro-and-in-vivo-antiviral-activities-against-amantadine-sensitive-and-resistant-influenza-a-viruses
#2
Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F Smee, William F DeGrado, Jun Wang
Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target...
January 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28081594/management-of-direct-antiviral-agent-failures
#3
REVIEW
María Buti, Rafael Esteban
The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). Most HCV patients treated with these drugs achieve viral elimination, but 1% to 15% fail to attain this objective. Treatment failures are usually related to relapse, and less often to on-treatment viral breakthrough. HCV drug resistant associated substitutions are detected in most patients who do not eliminate the virus. The risk of developing these variants depends on host- and virus-related factors, the properties of the drugs used, and the treatment strategies applied...
December 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28081470/inhibition-viral-rnp-and-anti-inflammatory-activity-of-coumarins-against-influenza-virus
#4
YuTao Wang, Wen Yan, QiaoLian Chen, WanYi Huang, Zifeng Yang, Xiong Li, XinHua Wang
Influenza viruses pose a severe threat to human health and a significant increase in antiviral drug-resistant among influenza viruses worldwide has been observed. Therefore, there is an urgent need to develop the new antiviral drugs, specifically from the natural products. In this study, the anti-viral and anti-inflammatory activities of coumarins against influenza A virus in vitro were investigated. One of the derivatives eleutheroside B1 showed a wide spectrum of anti- human influenza virus effect with the IC50 value of 64-125μg/ml in vitro, but it showed no effects against avian influenza virus...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28078813/host-defense-peptide-derived-privileged-scaffolds-for-anti-infective-drug-discovery
#5
Ersilia Nigro, Irene Colavita, Daniela Sarnataro, Olga Scudiero, Aurora Daniele, Francesco Salvatore, Antonello Pessi
'Privileged scaffolds' are molecular frameworks which have been successfully exploited for small molecule drug discovery. Peptide privileged scaffolds, featuring a strictly conserved multiple-disulfide framework and high variability in the rest of the sequence, display a broad range of biological effects, including antimicrobial and antiviral activity. Unlike small molecules, however, the cost of manufacturing these peptides is high, and their synthesis challenging. We previously described a simplified privileged scaffold corresponding to the γ-core of human β-defensin-3 (HBD3)...
January 12, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28078526/effectiveness-and-safety-of-entecavir-or-tenofovir-in-a-spanish-cohort-of-chronic-hepatitis-b-patients-validation-of-the-page-b-score-to-predict-hepatocellular-carcinoma
#6
Mar Riveiro-Barciela, David Tabernero, José L Calleja, Sabela Lens, María L Manzano, Francisco Gea Rodríguez, Javier Crespo, Belén Piqueras, Juan M Pascasio, Carmen Comas, Maria L Gutierrez, Alberto Aguirre, Emilio Suárez, Javier García-Samaniego, Miguel Rivero, Doroteo Acero, Miguel Fernandez-Bermejo, Diego Moreno, Pilar Sánchez-Pobre, Beatriz de Cuenca, J J Moreno-Palomares, Rafael Esteban, Maria Buti
BACKGROUND: Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The Page-B score could be useful to estimate the probability of HCC. AIMS: To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting. METHODS: Analysis of Caucasian chronic hepatitis B subjects treated with entecavir or tenofovir from the prospective, multicenter database CIBERHEP...
January 11, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28077314/biological-or-pharmacological-activation-of-protein-kinase-c-alpha-constrains-hepatitis-e-virus-replication
#7
Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrera Carrillo, Johannes H Brandsma, Raymond A Poot, Ben Berkhout, Johan Neyts, Maikel P Peppelenbosch, Qiuwei Pan
Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication...
January 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28075376/the-new-high-resolution-crystal-structure-of-ns2b-ns3-protease-of-zika-virus
#8
Syed Lal Badshah, Abdul Naeem, Yahia Mabkhot
Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article "Crystal structure of unlinked NS2B-NS3 protease from Zika virus" published recently in the journal Science by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed...
January 10, 2017: Viruses
https://www.readbyqxmd.com/read/28074358/genotype-3-infection-the-last-stand-of-hepatitis-c-virus
#9
Austin Chan, Keyur Patel, Susanna Naggie
Hepatitis C virus (HCV) represents a significant global disease burden, with an estimated 130-150 million people worldwide living with chronic HCV infection. Within the six major clinical HCV genotypes, genotype 3 represents 22-30% of all infection and is described as a unique entity with higher rates of steatosis, faster progression to cirrhosis, and higher rates of hepatocellular carcinoma. Hepatic steatosis in the setting of hepatitis C genotype 3 (HCV-3) is driven by viral influence on three major pathways: microsomal triglyceride transfer protein, sterol regulatory element-binding protein-1c, and peroxisome proliferator-associated receptor-α...
January 10, 2017: Drugs
https://www.readbyqxmd.com/read/28074089/antiviral-activity-of-animal-venom-peptides-and-related-compounds
#10
REVIEW
Élida Cleyse Gomes da Mata, Caroline Barbosa Farias Mourão, Marisa Rangel, Elisabeth Ferroni Schwartz
Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28073762/a-dna-intercalation-methodology-for-an-efficient-prediction-of-ligand-binding-pose-and-energetics
#11
Anjali Soni, Pooja Khurana, Tanya Singh, B Jayaram
MOTIVATION: Drug intercalation is an important strategy for DNA inhibition which is often employed in cancer chemotherapy. Despite its high significance, the field is characterized by limited success in identification of novel intercalator molecules and lack of automated and dedicated drug-DNA intercalation methodology. RESULTS: We report here a novel intercalation methodology (christened 'Intercalate') for predicting both the structures and energetics of DNA-intercalator complexes, covering the processes of DNA unwinding and (non-covalent) binding...
January 10, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28072684/assessment-of-hepatocellular-carcinoma-risk-based-on-peg-interferon-plus-ribavirin-treatment-experience-in-this-new-era-of-highly-effective-oral-antiviral-drugs
#12
Seung Ho Lee, Young-Joo Jin, Jun Young Shin, Jin-Woo Lee
In this new era of highly effective oral antiviral drugs for chronic hepatitis C virus (HCV), indications for antiviral treatment may be extendable. This study undertaken to identify suitable candidates for peg-interferon plus ribavirin (PEG-IFN/RBV) treatment by evaluating hepatocellular carcinoma (HCC) risk in patients with chronic HCV treated or not with PEG-IFN/RBV.This large-scale retrospective study was conducted on 1176 patients with chronic HCV without a history of HCC (treatment group [n = 489] and no-treatment group [n = 687])...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28070753/dodecyl-amino-glucoside-enhances-transdermal-and-topical-drug-delivery-via-reversible-interaction-with-skin-barrier-lipids
#13
Monika Kopečná, Miloslav Macháček, Eva Prchalová, Petr Štěpánek, Pavel Drašar, Martin Kotora, Kateřina Vávrová
PURPOSE: Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. METHODS: To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. RESULTS: Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer...
January 9, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28070174/the-hcv-treatment-revolution-continues-resistance-considerations-pangenotypic-efficacy-and-advances-in-challenging-populations
#14
Ira M Jacobson
The US Food and Drug Administration has now approved 10 direct-acting antivirals (DAAs) for the management of hepatitis C virus (HCV). These therapies are combined into 6 regimens that are given for varying durations, with or without ribavirin, depending on the viral genotype, the presence or absence of baseline resistance-associated variants (RAVs), and the patient type. RAVs may be present before exposure to a drug or may become detectable de novo during exposure to a drug. Emerging resistant strains are the most common cause of failure of HCV DAA regimens...
October 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28069912/idiosyncratic-drug-induced-neutropenia-agranulocytosis
#15
Emmanuel Andrès, Rachel Mourot-Cottet, Frédéric Maloisel, François Séverac, Olivier Keller, Thomas Vogel, Martine Tebacher, Jean-Christophe Weber, Georges Kaltenbach, Jacques-Eric Gottenberg, Bernard Goichot, Jean Sibilia, Anne-Sophie Korganow, Raoul Herbrecht
BACKGROUD: Few data is currently available on neutropenia and agranulocytosis related to drug intake. We report here data on 203 patients with established idiosyncratic drug-induced agranulocytosis, followed up in a referral centre within a university hospital. PATIENTS AND METHODS: Data from 203 patients with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis in the Strasbourg University Hospital (Strasbourg, France) RESULTS: : The mean age was 61...
January 9, 2017: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28068627/thiosemicarbazones-and-phthalyl-thiazoles-compounds-exert-antiviral-activity-against-yellow-fever-virus-and-saint-louis-encephalitis-virus
#16
Carolina Colombelli Pacca, Rafael Elias Marques, José Wanderlan P Espindola, Gevânio B O Oliveira Filho, Ana Cristina Lima Leite, Mauro Martins Teixeira, Mauricio L Nogueira
Arboviruses, arthropod-borneviruses, are frequency associated to human outbreak and represent a serious health problem. The genus Flavivirus, such as Yellow Fever Virus (YFV) and Saint Louis Encephalitis Virus (SLEV), are important pathogens with high morbidity and mortality worldwide. In Brazil, YFV is maintained in sylvatic cycle, but many cases are notified annually, despite the efficiency of vaccine. SLEV causes an acute encephalitis and is widely distributed in the Americas. There is no specific antiviral drugs for these viruses, only supporting treatment that can alleviate symptoms and prevent complications...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28068604/2-8-bis-trifluoromethyl-quinoline-analogs-show-improved-anti-zika-virus-activity-compared-to-mefloquine
#17
Giselle Barbosa-Lima, Adriana M Moraes, Adriele da S Araújo, Emerson T da Silva, Caroline S de Freitas, Yasmine R Vieira, Andressa Marttorelli, José Cerbino Neto, Patrícia T Bozza, Marcus V N de Souza, Thiago Moreno L Souza
Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine...
December 30, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28068304/benefits-of-high-dose-steroid%C3%A2-%C3%A2-hespander%C3%A2-%C3%A2-mannitol-administration-in-the-treatment-of-bell-s-palsy
#18
Takatoshi Furukawa, Yasuhiro Abe, Tsukasa Ito, Toshinori Kubota, Seiji Kakehata
OBJECTIVE: Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center...
February 2017: Otology & Neurotology
https://www.readbyqxmd.com/read/28067632/hcv-genotype-1-subtypes-and-resistance-associated-substitutions-in-drug-naive-and-in-direct-acting-antiviral-treatment-failure-patients
#19
Yael Gozlan, Ziv Ben-Ari, Roy Moscona, Rachel Shirazi, Avia Rakovsky, Arij Kabat, Ella Veizman, Tania Berdichevski, Peretz Weiss, Oranit Cohen-Ezra, Yoav Lurie, Inna Gafanovich, Marius Braun, Michal Cohen-Naftaly, Amir Shlomai, Oren Shibolet, Ehud Zigmond, Eli Zuckerman, Michal Carmiel-Haggai, Assy Nimer, Rawi Hazzan, Yaakov Maor, Yona Kitay-Cohen, Yonat Shemer, Zipi Kra-Oz, Lisita Schreiber, Ofer Peleg, Ella Mendelson, Orna Mor
BACKGROUND: Direct-acting antiviral (DAA) treatment regimens and response rates of patients with hepatitis C virus (HCV) genotype 1 (GT1) are currently considered subtype-dependent. Identification of clinically relevant resistance-associated substitutions (RASs) in the NS3 and NS5A proteins at baseline and in DAA failures, may also impact clinical decisions. METHODS: In a multicenter cohort study (n=308), NS3 or NS5B sequencing (n=248) was used to discriminate between GT1 subtypes...
January 9, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28067324/the-in-vivo-efficacy-of-neuraminidase-inhibitors-cannot-be-determined-from-the-decay-rates-of-influenza-viral-titers-observed-in-treated-patients
#20
John Palmer, Hana M Dobrovolny, Catherine A A Beauchemin
Antiviral therapy is a first line of defence against new influenza strains. Current pandemic preparations involve stock- piling oseltamivir, an oral neuraminidase inhibitor (NAI), so rapidly determining the effectiveness of NAIs against new viral strains is vital for deciding how to use the stockpile. Previous studies have shown that it is possible to extract the drug efficacy of antivirals from the viral decay rate of chronic infections. In the present work, we use a nonlinear mathematical model representing the course of an influenza infection to explore the possibility of extracting NAI drug efficacy using only the observed viral titer decay rates seen in patients...
January 9, 2017: Scientific Reports
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