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Antiviral Chemistry & Chemotherapy

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https://www.readbyqxmd.com/read/27815332/novel-symmetrical-phenylenediamines-as-potential-anti-hepatitis-c-virus-agents
#1
Marcella Bassetto, Salvatore Ferla, Pieter Leyssen, Johan Neyts, Mark M Yerukhimovich, David N Frick, Rachel O'Donnell, Andrea Brancale
BACKGROUND: Despite the great progress made in the last 10 years, alternative strategies might help improving definitive treatment options against hepatitis C virus infection. METHODS: With the aim of identifying novel inhibitors of the hepatitis C virus-1b replication targeting the viral NS3 helicase, the structures of previously reported symmetrical inhibitors of this enzyme were rationally modified, and according to docking-based studies, four novel scaffolds were selected for synthesis and evaluation in the hepatitis C virus-1b subgenomic replicon assay...
November 4, 2016: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27815331/anti-enteroviral-triple-combination-of-viral-replication-inhibitors-activity-against-coxsackievirus-b1-neuroinfection-in-mice
#2
Adelina Stoyanova, Ivanka Nikolova, Gerhard Pürstinger, Georgi Dobrikov, Vladimir Dimitrov, Stefan Philipov, Angel S Galabov
BACKGROUND: Chemotherapy is an important tool for controlling enterovirus infections, but clinically effective anti-enterovirus drugs do not currently exist, mainly due to the development of drug resistance. We investigated the combination effects of enterovirus replication inhibitors in order to limit this process. In previous studies, we showed the efficacy of consecutive alternating administration of the triple combinations disoxaril/guanidine/oxoglaucine and pleconaril/guanidine/oxoglaucine against coxsackievirus B1 infection in newborn mice...
November 4, 2016: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27620888/effect-of-sialidase-fusion-protein-das-181-on-human-metapneumovirus-infection-of-hep-2-cells
#3
Sutthiwan Thammawat, Tania A Sadlon, Penelope Adamson, David L Gordon
: Human metapneumovirus is an emerging cause of lower respiratory disease in infants, young children, and immunocompromised adults. We have previously demonstrated that human metapneumovirus infection is mediated by interaction of human metapneumovirus attachment (G) and/or fusion (F) proteins with cellular glycosaminoglycans. We report here the activity of an investigational sialidase fusion protein, DAS181, on human metapneumovirus infection of Hep-2 cells. These results suggest that human metapneumovirus infection may involve sialic acids, providing a new therapeutic strategy for human metapneumovirus for which there is currently no available treatment...
September 12, 2016: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27503576/isolation-and-characterization-of-hepatitis-c-virus-resistant-to-a-novel-phenanthridinone-derivative
#4
Wataru Ito, Masaaki Toyama, Mika Okamoto, Masanori Ikeda, Koichi Watashi, Takaji Wakita, Yuichi Hashimoto, Masanori Baba
BACKGROUND: The novel phenanthridinone derivative HA-719 has recently been identified as a highly potent and selective inhibitor of hepatitis C virus replication. To elucidate its mechanism of inhibition, we have isolated and analyzed a clone of hepatitis C virus replicon cells resistant to HA-719. METHODS: To isolate HA-719-resistant replicon cells, Huh-7 cells containing subgenomic hepatitis C virus replicons (genotype 1b) with a luciferase reporter (LucNeo#2) were cultured in the presence of G418 and escalating concentrations of HA-719...
August 8, 2016: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27503577/melatonin-decreases-brain-apoptosis-oxidative-stress-and-cd200-expression-and-increased-survival-rate-in-mice-infected-by-venezuelan-equine-encephalitis-virus
#5
Milagros Montiel, Ernesto Bonilla, Nereida Valero, Jesús Mosquera, Luz M Espina, Yasmir Quiroz, Melchor Álvarez-Mon
BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine encephalitis virus infection could lead to apoptosis and induce anti-inflammatory responses (increased expression of CD200). The aim of this study was to determine the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis virus. METHODS: Mice were infected with 10 median lethal doses (LD50) of Venezuelan equine encephalitis virus, treated with melatonin (500 µg/kg bw; three days before infection and during all experimental time) and sacrificed on days 1, 3, and 5 postinfection...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27341844/combination-activity-of-neuraminidase-inhibitor-oseltamivir-and-%C3%AE-tocopherol-in-influenza-virus-a-h3n2-infection-in-mice
#6
Angel S Galabov, Milka Mileva, Lora Simeonova, Galina Gegova
BACKGROUND: Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis-viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. METHODS: After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27296393/predicting-zika-virus-structural-biology-challenges-and-opportunities-for-intervention
#7
Bryan D Cox, Richard A Stanton, Raymond F Schinazi
BACKGROUND: Zika virus is an emerging crisis as infection is implicated in severe neurological disorders-Guillain-Barré syndrome and fetal microcephaly. There are currently no treatment options available for Zika virus infection. This virus is part of the flavivirus genus and closely related to Dengue Fever Virus, West Nile Virus, and Japanese Encephalitis Virus. Like other flaviviruses, the Zika virus genome encodes three structural proteins (capsid, precursor membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5)...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/27022094/derivatives-of-usnic-acid-inhibit-broad-range-of-influenza-viruses-and-protect-mice-from-lethal-influenza-infection
#8
A A Shtro, V V Zarubaev, O A Luzina, D N Sokolov, N F Salakhutdinov
BACKGROUND: Influenza is a disease of significant morbidity and mortality, the number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. In this work, we demonstrate activity of some usnic acid (UA) derivatives against influenza virus in vitro and in vivo. METHODS: Organic synthesis was used to prepare compounds. Antiviral activity of the compounds in vitro was evaluated by their ability to decrease the virus titer on Madin-Darby Canine Kidney cells...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26759268/molecular-basis-of-influenza-hemagglutinin-inhibition-with-an-entry-blocker-peptide-by-computational-docking-and-mass-spectrometry
#9
Robert Lu, Patrick Müller, Kevin M Downard
BACKGROUND: The increased resistance of circulating strains to current antiviral inhibitors of the influenza virus necessitates that new antivirals and their mode of action are identified. Influenza hemagglutinin is an ideal target given inhibitors of its function can block the entry of the virus into host cells during the early stages of replication. This article describes the molecular basis for the inhibition of H1 and H5 hemagglutinin by an entry-blocker peptide using companion molecular docking and mass spectrometry-based experiments...
August 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26527820/anti-hiv-1-activity-determined-by-%C3%AE-galactosidase-activity-in-the-multinuclear-activation-of-an-indicator-assay-is-comparable-with-that-by-a-conventional-focus-counting-method
#10
COMPARATIVE STUDY
Fusako Miyamoto, Kumi Kawaji, Shinya Oishi, Nobutaka Fujii, Mitsuo Kaku, Eiichi N Kodama
BACKGROUND: Direct comparison of enzymatic and original blue cell-counting detections with the multinuclear activation of an indicator (MAGI) cells, so far, remains to be performed in parallel. Although inhibitors for reverse transcription solely inhibit the reverse transcription step, those for HIV-1 entry block syncytium formation of HIV-1-infected MAGI cells in addition to the entry (dual inhibition). It raises a concern that reduction of enzymatic activity is artificially influenced by syncytium-blocking activity of inhibitors for entry...
April 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26514833/design-synthesis-and-anti-hiv-1-activity-of-1-substituted-3-3-5-dimethylbenzyl-triazine-derivatives
#11
Norikazu Sakakibara, Gianfranco Balboni, Cenzo Congiu, Valentina Onnis, Yosuke Demizu, Takashi Misawa, Masaaki Kurihara, Yoshihisa Kato, Tokumi Maruyama, Masaaki Toyama, Mika Okamoto, Masanori Baba
BACKGROUND: The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is an attractive target for the development of drugs used in the treatment of HIV-1 infection and acquired immune deficiency syndrome (AIDS). We have continued the search for novel anti-HIV-1 agents using the structure-activity relationships of the successful 1,3-disubstituted and 1,3,6-trisubstituted uracil-type HIV-1 RT inhibitors. METHODS: A series of new triazine analogs were synthesized using an established method...
April 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26463822/prodrugs-of-herpes-simplex-thymidine-kinase-inhibitors
#12
Milka Yanachkova, Wei-Chu Xu, Sofya Dvoskin, Edward J Dix, Ivan B Yanachkov, Federico Focher, Lida Savi, M Dulfary Sanchez, Timothy P Foster, George E Wright
BACKGROUND: Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model. METHODS: Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug...
April 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26229068/a-two-week-regimen-of-high-dose-integrase-inhibitors-does-not-cause-nephrotoxicity-in-mice
#13
Michael T Eadon, Hongji Zhang, Todd C Skaar, Takashi Hato, Pierre C Dagher, Samir K Gupta, Zeruesenay Desta
BACKGROUND: The integrase inhibitors, raltegravir and dolutegravir, are nucleoside reverse transcriptase inhibitor-sparing agents which may be used as part of first-line antiretroviral therapy for HIV. These drugs inhibit creatinine secretion through organic cation transporters, thus elevating serum creatinine without affecting glomerular filtration. We sought to determine whether subtle signs of nephrotoxicity could be observed in mice administered a two-week regimen of high-dose integrase inhibitors...
April 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26071135/exploration-of-the-anti-enterovirus-activity-of-a-series-of-pleconaril-pirodavir-like-compounds
#14
Angela Bernard, Céline Lacroix, Maria G Cabiddu, Johan Neyts, Pieter Leyssen, Raffaello Pompei
BACKGROUND: The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication...
April 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26149265/influence-of-l-lysine-amino-acid-on-the-hiv-1-rna-replication-in%C3%A2-vitro
#15
Evgeny Vlad Butorov
BACKGROUND: Virus replication strongly depends on host metabolic machinery and essential cellular factors, in particular, on amino acid profiles. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways, including gene expression. The inhibitory effects of deficiency or excess of these essential elements on virus replication are widely appreciated. Although the same interrelationship between host cellular factors and HIV have been recognized for a long time, the effects of amino acids on HIV-1 RNA replication dynamic is not yet well documented...
February 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26149264/identification-of-a-dibenzocyclooctadiene-lignan-as-a-hiv-1-non-nucleoside-reverse-transcriptase-inhibitor
#16
Ying-Shan Han, Wei-Lie Xiao, Hongtao Xu, Victor G Kramer, Yudong Quan, Thibault Mesplède, Maureen Oliveira, Susan P Colby-Germinario, Han-Dong Sun, Mark A Wainberg
BACKGROUND: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. METHODS: HIV-1 inhibitors were identified and biologically characterized for mechanism of action. RESULTS: We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays...
February 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26149263/efficacy-of-n-methanocarbathymidine-against-genital-herpes-simplex-virus-type-2-shedding-and-infection-in-guinea-pigs
#17
David I Bernstein, Fernando J Bravo, Derek A Pullum, Hui Shen, Mei Wang, Aquilur Rahman, Robert I Glazer, Rhonda D Cardin
BACKGROUND: Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases. METHODS: The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated...
February 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26149262/design-synthesis-and-anti-hiv-1-activity-of-1-aromatic-methyl-substituted-3-3-5-dimethylbenzyl-uracil-and-n-3-5-dimethylbenzyl-substituted-urea-derivatives
#18
Norikazu Sakakibara, Masanori Baba, Mika Okamoto, Masaaki Toyama, Yosuke Demizu, Takashi Misawa, Masaaki Kurihara, Kohji Irie, Yoshihisa Kato, Tokumi Maruyama
BACKGROUND: A new series of 1-aromatic methyl-substituted 3-(3,5-dimethylbenzyl)uracil and N-3,5-dimethylbenzyl-substituted urea derivatives were synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. METHODS: A series of new 6-azido and 6-amino derivatives of 1-substituted-3-(3,5-dimethylbenzyl)uracils were synthesized using our previously reported method, and three acyclic derivatives were synthesized from urea. The anti-HIV-1 activities of these compounds were determined based on the inhibition of virus-induced cytopathogenicity in MT-4 cells...
February 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/26149261/avcc-1990-2015-a-journal-to-combine-antiviral-biology-and-antiviral-chemistry-enters-the-third-era
#19
EDITORIAL
Hugh J Field
No abstract text is available yet for this article.
February 2015: Antiviral Chemistry & Chemotherapy
https://www.readbyqxmd.com/read/23744599/recent-findings-on-the-mechanisms-involved-in-tenofovir-resistance
#20
REVIEW
Pinar Iyidogan, Karen S Anderson
Since its approval for clinical use in 2001, tenofovir (TFV) has become one of the most frequently prescribed nucleotide analogues used in combination with other antiretroviral agents against HIV-1 infection. Although reverse transcriptase inhibitors (RTIs) including TFV have been shown to be highly potent with reasonable safety profiles in the clinic, drug resistance hinders the effectiveness of current therapies and even causes treatment failure. Therefore, understanding the resistance mechanisms of RT and exploring the potential antiviral synergy between the different RTIs in combination therapies against the resistance mechanisms would greatly improve the long-term efficacy of existing and future regimens...
December 16, 2014: Antiviral Chemistry & Chemotherapy
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