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ANTIVIRAL DRUGS

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https://www.readbyqxmd.com/read/28220872/human-enterovirus-71-protein-interaction-network-prompts-antiviral-drug-repositioning
#1
Lu Han, Kang Li, Chaozhi Jin, Jian Wang, Qingjun Li, Qiling Zhang, Qiyue Cheng, Jing Yang, Xiaochen Bo, Shengqi Wang
As a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (EV71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. Although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, EV71-host protein interactions have not been explored...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219799/uplc-ms-ms-method-for-the-simultaneous-quantification-of-three-new-antiretroviral-drugs-dolutegravir-elvitegravir-and-rilpivirine-and-other-thirteen-antiretroviral-agents-plus-cobicistat-and-ritonavir-boosters-in-human-plasma
#2
Marco Simiele, Alessandra Ariaudo, Amedeo De Nicolò, Fabio Favata, Martina Ferrante, Chiara Carcieri, Stefano Bonora, Giovanni Di Perri, Antonio De Avolio
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs. In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28219047/strategies-in-the-designing-of-prodrugs-taking-into-account-the-antiviral-and-anticancer-compounds
#3
REVIEW
Monika A Lesniewska-Kowiel, Izabela Muszalska
Prodrugs are a wide group of substances of low or no pharmacological activity. The search for prodrugs is aimed at obtaining drugs characterized by better pharmacokinetic properties, pharmaceutical availability and selective activity of the active substance. Prodrug strategies involve chemical modifications and syntheses of new structures as well as the establishment of systems that deliver active substances for therapeutic aims that is prodrug-based treatments. The paper describes decisive factors in prodrug designing, such as enzymes participating in their activation, concepts of chemical modifications in the group of antiviral drugs and new anticancer treatments based on prodrugs (ADEPT, GDEPT, LEAPT)...
February 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28218730/neoflavonoids-as-inhibitors-of-hiv-1-replication-by-targeting-the-tat-and-nf-%C3%AE%C2%BAb-pathways
#4
Dionisio A Olmedo, José Luis López-Pérez, Esther Del Olmo, Luis M Bedoya, Rocío Sancho, José Alcamí, Eduardo Muñoz, Arturo San Feliciano, Mahabir P Gupta
Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 μM...
February 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28216367/identification-and-evaluation-of-potent-middle-east-respiratory-syndrome-coronavirus-mers-cov-3cl-pro-inhibitors
#5
Vathan Kumar, Jin Soo Shin, Jiun-Jie Shie, Keun Bon Ku, Chonsaeng Kim, Yun Young Go, Kai-Fa Huang, Meehyein Kim, Po-Huang Liang
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory illness with fever, cough and shortness of breath. Up to date, it has resulted in 1826 human infections, including 649 deaths. Analogous to picornavirus 3C protease (3C(pro)), 3C-like protease (3CL(pro)) is critical for initiation of the MERS-CoV replication cycle and is thus regarded as a validated drug target. As presented here, our peptidomimetic inhibitors of enterovirus 3C(pro) (6b, 6c and 6d) inhibited 3CL(pro) of MERS-CoV and severe acute respiratory syndrome coronavirus (SARS-CoV) with IC50 values ranging from 1...
February 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28216196/hypericum-perforatum-st-john-s-wort-beyond-depression-a-therapeutic-perspective-for-pain-conditions
#6
REVIEW
Nicoletta Galeotti
ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L. (Hypericaceae), popularly called St. John's wort (SJW), has a rich historical background being one of the oldest used and most extensively investigated medicinal herbs. Many bioactivities and applications of SJW are listed in popular and in scientific literature, including antibacterial, antiviral, anti-inflammatory. In the last three decades many studies focused on the antidepressant activity of SJW extracts. However, several studies in recent years also described the antinociceptive and analgesic properties of SJW that validate the traditional uses of the plant in pain conditions...
February 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28215167/chemical-modifications-of-ketoprofen-nsaid-in-search-of-better-lead-compounds-a-review-of-literature-from-2004-2016
#7
Gita Chawla, Chanda Ranjan, Anees A Siddiqui, Jagdish Kumar, Ankita Pathak
BACKGROUND: Ketoprofen, a potent anti-inflammatory, analgesic and anti-pyretic drug belonging to the propionic acid class was synthesized in 1968. Rapid absorption, simple metabolism, faster blood brain barrier crossing and high antinociceptive activity are the features responsible for its high use. But, free acidic moiety present in its structure is the major factor that declines its popularity by causing various gastric side effects .Many researchers have chemically modified this drug with the aim to discover an improved and safe NSAID candidate or a new drug with altered activity...
February 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28215152/biological-activities-of-sesquiterpene-lactones-isolated-from-the-genus-centaurea-l-asteraceae
#8
Marina Sokovic, Ana Ciric, Jasmina Glamoclija, Helen Skaltsa
BACKGROUND: In recent years, a growing interest has developed in the field of biological activity of plant metabolites. Research in this area considering antimicrobial, antioxidant, cytotoxic, anti-inflammatory, and other properties, is currently expanding, reporting various species to possess such biological effects. Among them, Centaurea species are well known to be used in ethnomedicine. The Centaurea genus (Asteraceae) is represented by more than 500 species, mostly located in the Mediterranean region and Western Asia...
February 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28215138/amino-acid-ester-prodrugs-of-nucleoside-and-nucleotide-antivirals
#9
Marcela Krečmerová
The review covers basic principles of the prodrug strategy applied to antiviral nucleoside drugs or drug candidates. Specific role of amino acids as promoieties is explained with respect to transport mechanisms, pharmacokinetics and a low toxicity of compounds. Synthetic approaches to the most important representatives (compounds under clinical investigations or available on the market) are described, including valacyclovir, valganciclovir, valomaciclovir stearate, valcyclopropavir, valtorcitabine, valopicitabine and several attempts to amino acid modifications of antiretroviral nucleosides...
February 16, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28213871/thieno-2-3-b-pyridine-derivatives-a-new-class-of-antiviral-drugs-against-mayaro-virus
#10
Raquel Amorim, Marcelo Damião Ferreira de Meneses, Julio Cesar Borges, Luiz Carlos da Silva Pinheiro, Lucio Ayres Caldas, Claudio Cesar Cirne-Santos, Marcos Vinícius Palmeira de Mello, Alessandra Mendonça Teles de Souza, Helena Carla Castro, Izabel Christina Nunes de Palmer Paixão, Renata de Mendonça Campos, Ingrid E Bergmann, Viviana Malirat, Alice Maria Rolim Bernardino, Moacyr Alcoforado Rebello, Davis Fernandes Ferreira
Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line...
February 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28213381/outcomes-of-treatment-with-direct-acting-antivirals-for-infection-with-hepatitis-c-virus-genotypes-1-4-in-an-ambulatory-care-setting
#11
Timothy A Bach, Kathy Zaiken
PURPOSE: Outcomes with direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) genotypes 1-4 were determined. METHODS: A total of 360 patients at 36 clinical sites in Massachusetts with HCV genotypes 1-4 and a prescription for at least one DAA medication between May 2011 and October 2015 were included. The primary investigator completed a retrospective and concurrent chart review, and data were collected through April 2016. RESULTS: A total of 446 patients were assessed for eligibility into the study, with 86 patients excluded...
March 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28212220/hcv-antiviral-therapy-in-liver-transplant-candidates-and-recipients-with-renal-insufficiency
#12
Elizabeth C Verna, Robert S Brown
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world, and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective directly active antiviral (DAA) therapy, such that most patients can be cured in the pre or posttransplant setting. In addition, there are now DAA regimens specifically approved for use in patients with severe renal insufficiency...
February 16, 2017: Transplantation
https://www.readbyqxmd.com/read/28208098/-don-t-think-i-m-going-to-leave-you-over-it-accounts-of-changing-hepatitis-c-status-among-couples-who-inject-drugs
#13
Jake Rance, Carla Treloar, Suzanne Fraser, Joanne Bryant, Tim Rhodes
BACKGROUND: While the health-related benefits of intimate partnership are well documented, little attention has been paid to couples exposed to high levels of social stigma and exclusion. In this project we investigated an important site of stigma for partnerships by collecting accounts of changing hepatitis C (HCV) status ("sero-change") among couples that inject drugs. We explored what these accounts reveal about the meaning of HCV for these couples, and how this understanding contributes to our collective efforts at prevention and care...
January 31, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28207898/distinct-susceptibility-and-applicability-of-mdck-derivatives-for-influenza-virus-research
#14
Shih-Chao Lin, Matthew A Kappes, Mei-Chun Chen, Chi-Chen Lin, Tony T Wang
Madin-Darby Canine Kidney (MDCK) cells are widely utilized as a substrate for influenza virus isolation and propagation due to the high yields of virus. Here we compared the conventional MDCK cell line, MDCK-SIAT1 and MDCK-London for viral production, cell survival, and suitability in testing antivirals using six influenza strains including two H1N1 (pandemic and epidemic strains), three H3N2 and one influenza B strain. Overall our results suggest that MDCK-London cell line is superior for virus culturing and quantification, and hence an ideal platform to evaluate antiviral drug efficacy against multiple strains of influenza...
2017: PloS One
https://www.readbyqxmd.com/read/28205403/functionalized-calix-4-arenes-as-potential-therapeutic-agents
#15
Muhammad Moazzam Naseer, Mukhtiar Ahmed, Shahid Hameed
Calixarenes, composed of phenolic units linked by methylene bridges at the 2,6-positions, represent a versatile class of macrocyclic compounds in supramolecular chemistry that can host small molecules or ions in their well-defined hydrophobic cavities. In recent years, it has been recognized that this class of compounds has the potential to serve as platform for the design of biological active compounds. Therefore, the calixarenes functionalized with different pharmacophoric groups have been synthesized as target structure by many researchers and were further evaluated for their biological activities...
February 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28205288/hematological-adverse-effects-and-pharmacokinetics-of-ribavirin-in-pigs-following-intramuscular-administration
#16
D-U Lee, S H Je, S J Yoo, T Kwon, J Y Shin, J J Byun, J-H Park, K-W Jeong, J-M Ku, Y S Lyoo
Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections...
February 15, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28203449/a-cost-utility-analysis-of-different-antiviral-medicine-regimens-in-patients-with-chronic-hepatitis-c-virus-genotype-1-infection
#17
Seyed Moayed Alavian, Shekoufeh Nikfar, Abbas Kebriaeezadeh, Farhad Lotfi, Ehsan Sanati, Mohsen Rezaei Hemami, Khosro Keshavarz
BACKGROUND: Despite the introduction of new drug regimens with high effectiveness for the hepatitis C virus (HCV) patients, especially in HCV genotype 1, no cost-effectiveness study on the selection of the superior drug strategy in Iran has been conducted yet. OBJECTIVES: This study is aimed to assess the cost-effectiveness of the three drug regimens of pegylated interferon and ribavirin (PR), sofosbuvir (SOF) + PR and ledipasvir and sofosbuvir (LDV/SOF) in patients with HCV genotype 1 in Iran in the year 2014...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28202793/the-new-aptima-hbv-quant-real-time-tma-assay-accurately-quantifies-hepatitis-b-virus-dna-from-genotypes-a-to-f
#18
Stéphane Chevaliez, Claude Dauvillier, Fabienne Dubernet, Jean-Dominique Poveda, Syria Laperche, Christophe Hézode, Jean-Michel Pawlotsky
Sensitive and accurate hepatitis B virus (HBV) DNA detection and quantification are essential to diagnose HBV infection, establish the prognosis of HBV-related liver disease, guide the decision to treat and monitor the virological response to antiviral treatment and the emergence of resistance. Currently available HBV DNA platforms and assays are generally designed for batching multiple specimens within an individual run and require at least one full day of work to complete the analyses. The aim of this study was to evaluate the ability of the newly developed, fully automated, one-step Aptima HBV Quant assay to accurately detect and quantify HBV DNA in a large series of patients infected with different HBV genotypes...
February 15, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28202763/inhibition-of-vpx-mediated-samhd1-and-vpr-mediated-hltf-degradation-by-selective-disruption-of-viral-crl4-dcaf1-e3-ubiquitin-ligase-assembly
#19
Hong Wang, Haoran Guo, Jiaming Su, Yajuan Rui, Wenwen Zheng, Wenying Gao, Wenyan Zhang, Zhaolong Li, Guanchen Liu, Wei Wei, Xiao-Fang Yu
The lentiviral accessory proteins Vpx and Vpr are known to utilize CRL4 (DCAF1) E3 ligase to induce the degradation of the host restriction factor SAMHD1 or transcriptional factor HLTF, respectively. Selective disruption of viral CRL4 (DCAF1) E3 ligase could be a promising antiviral strategy. Recently, we have determined that post-translational modification (neddylation) of Cullin-4 is required for the activation of Vpx-CRL4 (DCAF1) E3 ligase. However, the mechanism of Vpx/Vpr-CRL4 (DCAF1) E3 ligase assembly is still poorly understood...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202375/generation-and-characterization-of-west-nile-pseudo-infectious-reporter-virus-for-antiviral-screening
#20
Hong-Lei Zhang, Han-Qing Ye, Cheng-Lin Deng, Si-Qing Liu, Pei-Yong Shi, Cheng-Feng Qin, Zhi-Ming Yuan, Bo Zhang
West Nile virus (WNV), a mosquito-borne flavivirus, is an important neurotropic human pathogen. As a biosafety level-3 (BSL-3) agent, WNV is strictly to BSL-3 laboratories for experimentations, thus greatly hindering the development of vaccine and antiviral drug. Here, we developed a novel pseudo-infectious WNV reporter virus expressing the Gaussia luciferase (Gluc). A stable 293TNS1 cell line expressing NS1 was selected for trans-supplying NS1 protein to support the replication of WNV-ΔNS1 virus and WNV-ΔNS1-Gluc reporter virus with large-fragment deletion of NS1...
February 12, 2017: Antiviral Research
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