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https://www.readbyqxmd.com/read/30315899/identification-of-dna-methylation-regulated-novel-host-genes-relevant-to-inhibition-of-virus-replication-in-porcine-pk15-cell-using-double-stranded-rna-mimics-and-dna-methyltransferase-inhibitor
#1
Xiaoshuo Wang, Hong Ao, Minyan Song, Lijing Bai, Weiyong He, Chuduan Wang, Ying Yu
During RNA viruses's replication, double-stranded RNA (dsRNA) is normally produced and induce host innate immune response. Most of gene activation due cytokine mediated but which are due to methylation mediated is still unknown. In the study, DNA methylome was integrated with our previous transcriptome data to investigate the differentially methylated regions and genes using MeDIP-chip technology. We found that the transcriptional expressions of 15, 37 and 18 genes were negatively related with their promoter DNA methylation levels in the cells treated by PolyI:C, Aza-CdR, as well as PolyI:C plus Aza-CdR, respectively, compared with the untreated cells...
October 10, 2018: Genomics
https://www.readbyqxmd.com/read/30315877/structures-of-zika-virus-ns2b-ns3-protease-in-complex-with-peptidomimetic-inhibitors
#2
Wint Wint Phoo, Zhenzhen Zhang, Melissa Wirawan, Edwin Chew Jun Chen, Chew Bing Liang Alvin, Jenny Kouretova, Torsten Steinmetzer, Dahai Luo
Zika virus NS2B-NS3 protease plays an essential role in viral replication by processing the viral polyprotein into individual proteins. The viral protease is therefore considered as an ideal antiviral drug target. To facilitate the development of protease inhibitors, we report three high-resolution co-crystal structures of bZiPro with peptidomimetic inhibitors composed of a P1-P4 segment and different P1' residues. Compounds 1 and 2 possess small P1' groups that are cleaved by bZiPro, which could be detected by mass spectrometry...
October 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30315876/substituted-3-benzylcoumarins-13-and-14-suppress-enterovirus-a71-replication-by-impairing-viral-2a-pro-dependent-ires-driven-translation
#3
Hao Zhang, Xin Wang, Yuya Wang, Xinyi Pei, Chao Wang, Yan Niu, Ping Xu, Yihong Peng
Activation of the ERK signaling cascade in host cells has been demonstrated to be essential for Enterovirus A71 (EV-A71) replication. Our previous study showed that MEK kinase, which specially activated downstream ERK kinase, is an important and potential target against EV-A71. Furthermore, we reported that a series of substituted 3-benzylcoumarins designed and synthesized as well as verified for inhibiting the MEK-ERK cascade were found to be effective on anti-EV-A71. In this study, we further demonstrated that two substituted 3-benzylcoumarins designated as 13 and 14 were more effective anti-MEK/ERK activity, less cytotoxicity and stronger antiviral effect represented by inhibition of viral-induced CPE, the expression of viral proteins and the replication of the viral genome, as well as the production of progeny virions, compared to those of U0126, an available MEK inhibitor, and sorafenib, a multiple-targeted kinase inhibitor in clinical use...
October 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30315623/unscheduled-hdac4-repressive-activity-in-human-fibroblasts-triggers-tp53-dependent-senescence-and-favours-cell-transformation
#4
Harikrishnareddy Paluvai, Eros Di Giorgio, Claudio Brancolini
Expression of the class IIa HDACs is frequently altered in different human cancers. In mouse models these transcriptional repressors can trigger transformation, acting as bona fide oncogenes. Whether class IIa HDACs also exhibit transforming activities in human cells is currently unknown. We infected primary human fibroblasts with retroviruses to investigate the transforming activity of HDAC4 in cooperation with well-known oncogenes. We have discovered that HDAC4-TM, a nuclear resident version of the deacetylase, triggers TP53 stabilization and OIS (Oncogene-induced senescence)...
October 13, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/30315192/antiretroviral-resistance-genotypic-characterization-and-origin-of-human-immunodeficiency-virus-among-the-infected-wives-of-intravenous-drug-users-in-manipur
#5
Adhikarimayum Lakhikumar Sharma, Thiyam Ramsing Singh, Lisam Shanjukumar Singh
Increasing incidence of drug resistance is ascertained to be the main obstacles in limiting the virus among the human immunodeficiency virus (HIV) infected individuals. This study investigates the drug resistance mutations (DRMs), genetic variants and origin of transmitted drug resistance of HIV-1 among the HIV-1 infected wives of intravenous drug users (IDUs) in Manipur. 44 HIV pol gene sequences were generated from 56 blood samples by viral gene amplification and sequencing. Sequences were then analysed for drug resistance, genetic variants and origin...
October 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30314470/virologic-suppression-in-response-to-antiretroviral-therapy-despite-extensive-resistance-within-hiv-1-reverse-transcriptase-after-the-first-virologic-failure
#6
Marta Iglis Oliveira, Valter Romão de Souza Junior, Claudia Fernanda de Lacerda Vidal, Paulo Sérgio Ramos de Araújo
BACKGROUND: Incomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks. METHODS: This work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers...
October 12, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/30311586/interferon-free-regimen-for-hepatitis-c-insight-and-management
#7
Muhammad Shareef Masoud, Usman Ali Ashfaq, Hina Khalid
The rapid development of direct-acting antiviral agents (DAA) for hepatitis C virus (HCV) therapy dramatically altered the treatment landscape of this disease. The DAA regimen is associated with various advantages including high sustained virological response (SVR) with minimum side effects and low pill load and specific inhibition of viral replication, which lowers dependence on the host cell. This regimen has substantially replaced conventional (interferon) therapy with high cure rates (> 90%) in most HCV populations...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/30311576/immunotherapy-for-ebv-associated-nasopharyngeal-carcinoma
#8
Mengying Hong, Kejun Tang, Jing Qian, Hongyu Deng, Musheng Zeng, Shu Zheng, Kefeng Ding, Yushen Du, Ren Sun
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is one of the most common head and neck malignancies in southern China and Southeast Asia. Unfortunately, 70% of NPC patients have locally advanced disease at the first diagnosis. Radiotherapy alone and concurrent chemoradiotherapy are important treatment approaches for NPC, but they have a limited effect on patients with locally advanced or distantly metastatic disease. 1-5 Nevertheless, the unique immune environment of the EBV-associated NPC provides rational targets for immunotherapy...
2018: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/30309895/activation-of-liver-x-receptor-plays-a-central-role-in-antiviral-actions-of-25-hydroxycholesterol
#9
Ying Liu, Zhuo Wei, Ye Zhang, Xingzhe Ma, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Youjia Cao, Jian Liu, Jihong Han, Xiaoxiao Yang, Yajun Duan
Production of 25-hydroxycholesterol (25HC), a potent inhibitor of viral infection, is catalyzed by cholesterol 25-hydroxylase (CH25H). We previously reported that 25HC induced CH25H expression in a liver X receptor (LXR)-dependent manner, implying that LXR can play an important role in antiviral infection. In this study, we determined that activation of LXR by 25HC or synthetic ligands (T0901317 or GW3965) inhibited infection of HSV-1 or MLV-(VSV)-GFP in HepG2 cells or RAW 264.7 macrophages. Genetic deletion of LXRα, LXRβ or CH25H expression in HepG2 cells by CRISPR/Cas9 method increased cell susceptibility to HSV-1 infection, and attenuated the inhibition of LXR on viral infection...
October 11, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/30309671/design-synthesis-biological-evaluation-and-cellular-imaging-of-imidazo-4-5-b-pyridine-derivatives-as-potent-and-selective-tam-inhibitors
#10
Tom Baladi, Jessy Aziz, Florent Dufour, Valentina Abet, Véronique Stoven, François Radvanyi, Florent Poyer, Ting-Di Wu, Jean-Luc Guerquin-Kern, Isabelle Bernard-Pierrot, Sergio Marco Garrido, Sandrine Piguel
The TAM kinase family arises as a new effective and attractive therapeutic target for cancer therapy, autoimmune and viral diseases. A series of 2,6-disubstituted imidazo[4,5-b]pyridines were designed, synthesized and identified as highly potent TAM inhibitors. Despite remarkable structural similarities within the TAM family, compounds 28 and 25 demonstrated high activity and selectivity in vitro against AXL and MER, with IC50 value of 0.77 nM and 9 nM respectively and a 120- to 900-fold selectivity. We also observed an unexpected nuclear localization for compound 10Bb, thanks to nanoSIMS technology, which could be correlated to the absence of cytotoxicity on three different cancer cell lines being sensitive to TAM inhibition...
September 25, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/30308992/wnt-%C3%AE-catenin-signaling-as-a-potential-target-for-the-treatment-of-liver-cirrhosis-using-antifibrotic-drugs
#11
REVIEW
Koji Nishikawa, Yosuke Osawa, Kiminori Kimura
Cirrhosis is a form of liver fibrosis resulting from chronic hepatitis and caused by various liver diseases, including viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, and autoimmune liver disease. Cirrhosis leads to various complications, resulting in poor prognoses; therefore, it is important to develop novel antifibrotic therapies to counter liver cirrhosis. Wnt/β-catenin signaling is associated with the development of tissue fibrosis, making it a major therapeutic target for treating liver fibrosis...
October 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30308963/a-novel-natural-influenza-a-h1n1-virus-neuraminidase-inhibitory-peptide-derived-from-cod-skin-hydrolysates-and-its-antiviral-mechanism
#12
Jianpeng Li, Yiping Chen, Ning Yuan, Mingyong Zeng, Yuanhui Zhao, Rilei Yu, Zunying Liu, Haohao Wu, Shiyuan Dong
In this paper, a novel natural influenza A H1N1 virus neuraminidase (NA) inhibitory peptide derived from cod skin hydrolysates was purified and its antiviral mechanism was explored. From the hydrolysates, novel efficient NA-inhibitory peptides were purified by a sequential approach utilizing an ultrafiltration membrane (5000 Da), sephadex G-15 gel column and reverse-phase high-performance liquid chromatography (RP-HPLC). The amino acid sequence of the pure peptide was determined by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) was PGEKGPSGEAGTAGPPGTPGPQGL, with a molecular weight of 2163 Da...
October 10, 2018: Marine Drugs
https://www.readbyqxmd.com/read/30308013/lamivudine-monotherapy-as-a-holding-regimen-for-hiv-positive-children
#13
Gabriela Patten, Jonathan Bernheimer, Lee Fairlie, Helena Rabie, Shobna Sawry, Karl Technau, Brian Eley, Mary-Ann Davies
BACKGROUND: In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. METHODS: We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history...
2018: PloS One
https://www.readbyqxmd.com/read/30306175/sulfono-%C3%AE-aa-modified-peptides-that-inhibit-hiv-1-fusion
#14
Olapeju Bolarinwa, Meng Zhang, Erin Mulry, Min Lu, Jianfeng Cai
The utilization of bioactive peptides in the development of highly selective and potent pharmacological agents for the disruption of protein-protein interactions is appealing for drug discovery. It is known that HIV-1 entry into a host cell is through a fusion process that is mediated by the trimeric viral glycoprotein gp120/41, which is derived from gp160 through proteolytic processing. Peptides derived from the HIV gp41 C-terminus have proven to be potent in inhibiting the fusion process. These peptides bind tightly to the hydrophobic pocket on the gp-41 N-terminus, which was previously identified as a potential inhibitor binding site...
October 11, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/30305383/limited-marginal-utility-of-deep-sequencing-for-hiv-drug-resistance-testing-in-the-age-of-integrase-inhibitors
#15
Ronit Dalmat, Negar Makhsous, Gregory Pepper, Amalia Magaret, Keith R Jerome, Anna Wald, Alexander L Greninger
HIV drug resistance genotyping is a critical tool in the clinical management of HIV infections. Although resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect lower frequency alleles. However, the clinical value added from NGS approaches to antiviral resistance testing remains to be demonstrated. We compared the variant detection capacity of NGS versus Sanger sequencing methods for resistance genotyping in 144 drug resistance tests (105 protease-reverse transcriptase tests and 39 integrase tests) submitted to our clinical virology laboratory over a four-month period in 2016 for Sanger-based HIV drug resistance testing...
October 10, 2018: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/30302352/real-world-experience-with-higher-than-recommended-doses-of-lamivudine-in-patients-with-varying-degrees-of-renal-impairment
#16
Briann Fischetti, Kushal Shah, David R Taft, Leonard Berkowitz, Anjali Bakshi, Agnes Cha
Background: Although nucleoside reverse transcriptase inhibitors have been associated with lactic acidosis, lamivudine (3TC) has not been reported to have an increased risk with elevated concentrations. Therefore, some recommend that the lowest tablet strength of 3TC be considered in patients with kidney disease to avoid the inconvenience of liquid formations. Our institution avoids dose-adjusting 3TC until creatinine clearance (CrCl) <30 mL/min and uses 100-150-mg tablets daily in hemodialysis...
October 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/30300716/micafungin-is-a-novel-anti-viral-agent-of-chikungunya-virus-through-multiple-mechanisms
#17
Yi-Jung Ho, Feng-Cheng Liu, Chia-Tsui Yeh, Chuen Mi Yang, Chang-Chi Lin, Te-Yu Lin, Po-Shiuan Hsieh, Ming-Kuan Hu, Zhiyuan Gong, Jeng-Wei Lu
The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans, which presents a serious global threat due to its high rate of contagion. The clinical symptoms of CHIKV include fever and persistent, severe arthritis. Micafungin has broad-spectrum fungicidal activity against Candida spp. is a promising echinocandin that was recently approved by the U.S. Food and Drug Administration (FDA) and has demonstrated activity against Candida and Aspergillus...
October 6, 2018: Antiviral Research
https://www.readbyqxmd.com/read/30299356/neuraminidase-inhibitor-resistance-in-influenza-a-clinical-perspective
#18
Nelson Lee, Aeron C Hurt
PURPOSE OF REVIEW: Neuraminidase inhibitors (NAIs), including oseltamivir, zanamivir, and peramivir, is the main class of antiviral available for clinical use. As such, development of resistance toward these agents is of great clinical and public health concern. RECENT FINDINGS: At present, NAI resistance remains uncommon among the circulating viruses (oseltamivir <3.5%, zanamivir <1%). Resistance risk is slightly higher in A(H1N1) than A(H3N2) and B viruses...
October 6, 2018: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/30298725/identification-of-myricetin-as-ebolavirus-vp35-dsrna-interaction-inhibitor-through-a-novel-fluorescence-based-assay
#19
Gian Luca Daino, Aldo Frau, Cinzia Sanna, Daniela Rigano, Simona Distinto, Veronica Madau, Francesca Esposito, Elisa Fanunza, Giulia Bianco, Orazio Taglialatela-Scafati, Luca Zinzula, Elias Maccioni, Angela Corona, Enzo Tramontano
The Filoviridae Ebola virus (EBOV) causes a severe and rapidly progressing hemorrhagic syndrome whose recent epidemic enlightened the urgent need of novel therapeutic agents, since no drug is currently approved. A key contribution to EBOV high lethality comes from viral evasion of the host antiviral innate immune response in which the viral protein VP35 plays a crucial role, blocking the interferon type I production, firstly by masking the viral dsRNA and preventing its detection by the pattern recognition receptor RIG-I...
October 9, 2018: Biochemistry
https://www.readbyqxmd.com/read/30297644/new-insights-into-development-of-transglutaminase-2-inhibitors-as-pharmaceutical-lead-compounds
#20
REVIEW
Soo-Youl Kim
Transglutaminase 2 (EC 2.3.2.13; TG2 or TGase 2) plays important roles in the pathogenesis of many diseases, including cancers, neurodegeneration, and inflammatory disorders. Under normal conditions, however, mice lacking TGase 2 exhibit no obvious abnormal phenotype. TGase 2 expression is induced by chemical, physical, and viral stresses through tissue-protective signaling pathways. After stress dissipates, expression is normalized by feedback mechanisms. Dysregulation of TGase 2 expression under pathologic conditions, however, can potentiate pathogenesis and aggravate disease severity...
October 8, 2018: Medical Sciences: Open Access Journal
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