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Antiviral Research

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https://www.readbyqxmd.com/read/28216367/identification-and-evaluation-of-potent-middle-east-respiratory-syndrome-coronavirus-mers-cov-3cl-pro-inhibitors
#1
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/28202376/structural-features-of-zika-virus-non-structural-proteins-3-and-5-and-its-individual-domains-in-solution-as-well-as-insights-into-ns3-inhibition
#2
Wuan Geok Saw, Ankita Pan, Malathy Sony Subramanian Manimekalai, Gerhard Grüber
Zika virus (ZIKV) has emerged as a pathogen of major health concern. The virus relies on its non-structural protein 5 (NS5) including a methyl-transferase (MTase) and a RNA-dependent RNA polymerase (RdRp) for capping and synthesis of the viral RNA and the nonstructural protein 3 (NS3) with its protease and helicase domain for polyprotein possessing, unwinding dsRNA proceeding replication, and NTPase/RTPase activities. In this study we present for the first time insights into the overall structure of the entire French Polynesia ZIKV NS3 in solution...
February 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28202375/generation-and-characterization-of-west-nile-pseudo-infectious-reporter-virus-for-antiviral-screening
#3
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
https://www.readbyqxmd.com/read/28192094/filovirus-proteins-for-antiviral-drug-discovery-structure-function-bases-of-the-replication-cycle
#4
REVIEW
Baptiste Martin, Bruno Canard, Etienne Decroly
Filoviruses are important pathogens that cause severe and often fatal hemorrhagic fever in humans, for which no approved vaccines and antiviral treatments are yet available. In an earlier article (Martin et al., Antiviral Research, 2016), we reviewed the role of the filovirus surface glycoprotein in replication and as a target for drugs and vaccines. In this review, we focus on recent findings on the filovirus replication machinery and how they could be used for the identification of new therapeutic targets and the development of new antiviral compounds...
February 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28188818/jnk1-2-inhibitor-reduces-dengue-virus-induced-liver-injury
#5
Gopinathan Pillai Sreekanth, Aporn Chuncharunee, Boonyarit Cheunsuchon, Sansanee Noisakran, Pa-Thai Yenchitsomanus, Thawornchai Limjindaporn
High viral load with liver injury is exhibited in severe dengue virus (DENV) infection. Mitogen activated protein kinases (MAPKs) including ERK1/2 and p38 MAPK were previously found to be involved in the animal models of DENV-induced liver injury. However, the role of JNK1/2 signaling in DENV-induced liver injury has never been investigated. JNK1/2 inhibitor, SP600125, was used to investigate the role of JNK1/2 signaling in the BALB/c mouse model of DENV-induced liver injury. SP600125-treated DENV-infected mice ameliorated leucopenia, thrombocytopenia, hemoconcentration, liver transaminases and liver histopathology...
February 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28185815/novel-antiviral-activity-and-mechanism-of-bromocriptine-as-a-zika-virus-ns2b-ns3-protease-inhibitor
#6
Jasper Fuk-Woo Chan, Kenn Ka-Heng Chik, Shuofeng Yuan, Cyril Chik-Yan Yip, Zheng Zhu, Kah-Meng Tee, Jessica Oi-Ling Tsang, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Gang Lu, Anna Jinxia Zhang, Kin-Kui Lai, Kwok-Hung Chan, Richard Yi-Tsun Kao, Kwok-Yung Yuen
Zika virus (ZIKV) infection is associated with congenital malformations in infected fetuses and severe neurological and other systemic complications in adults. There are currently limited anti-ZIKV treatment options that are readily available and safe for use in pregnancy. In this drug repurposing study, bromocriptine was found to have inhibitory effects on ZIKV replication in cytopathic effect inhibition, virus yield reduction, and plaque reduction assays. Time-of-drug-addition assay showed that bromocriptine exerted anti-ZIKV activity between 0 and 12 h post-ZIKV inoculation, corroborating with post-entry events in the virus replication cycle prior to budding...
February 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28179155/pre-and-post-pandemic-trends-in-antiviral-use-in-hospitalized-patients-with-laboratory-confirmed-influenza-2004-05-2013-14-toronto-canada
#7
Brenda L Coleman, Kazi Hassan, Karen Green, Jonathan B Gubbay, Kevin Katz, Tony Mazzulli, Shelly McNeil, Matthew Muller, Jeff Powis, David Richardson, Andrew Simor, Allison J McGeer
BACKGROUND: Data on factors associated with the use of antiviral medication to treat influenza in both children and adults are limited. OBJECTIVES: To describe trends in antiviral use, analyze factors associated with antiviral treatment of hospitalized patients with influenza, and to compare use based on guidelines. STUDY DESIGN: A retrospective observational cohort of hospitalized patients with laboratory confirmed influenza in southern Ontario hospitals for the 2004/05-2013/14 seasons...
February 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28163109/strategies-for-serum-chemokine-cytokine-assessment-as-biomarkers-of-therapeutic-response-in-hcv-patients-as-a-prototype-to-monitor-immunotherapy-of-infectious-diseases
#8
Erica Godinho Menezes, Jordana Grazziela Alves Coelho-Dos-Reis, Ludmila Melo Cardoso, Ágata Lopes-Ribeiro, Juan Jonathan-Gonçalves, Marco Túlio Porto Gonçalves, Rodrigo Dias Cambraia, Eric Bassetti Soares, Luciana Diniz Silva, Vanessa Peruhype-Magalhães, Maria Rios, Caren Chancey, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Rosângela Teixeira
In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL...
February 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28161581/characterization-of-a-thienylcarboxamide-derivative-that-inhibits-the-transactivation-functions-of-cytomegalovirus-ie2-and-varicella-zoster-virus-ie62
#9
Ryuichi Majima, Keiko Shindoh, Toyofumi Yamaguchi, Naoki Inoue
Previously we established reporter cell lines for human cytomegalovirus (HCMV) and varicella zoster virus (VZV) and identified several antiviral compounds against these viruses using the reporter cells. In this study, we found that one of the identified anti-HCMV compounds, a thienylcarboxamide derivative (coded as 133G4), was effective against not only HCMV but also VZV. The following findings indicate that 133G4 inhibits the activation of early gene promoters by HCMV IE2 and VZV IE62: i) 133G4 decreased the expression of HCMV early and late genes but not that of HCMV IE1/IE2 in HCMV-infected cells, ii) 133G4 inhibited the activation of several HCMV early gene promoters of transiently-transfected plasmids in HCMV-infected cells, and iii) in transient transfection assays, 133G4 decreased the activation of HCMV (or VZV) early gene promoters by HCMV IE2 (or VZV IE62) in the absence of other viral protein expression...
February 2, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28161580/the-ectodomain-of-rabies-virus-glycoprotein-determines-dendritic-cell-activation
#10
Junhua Huang, Yachun Zhang, Ying Huang, Clement W Gnanadurai, Ming Zhou, Ling Zhao, Zhen F Fu
The immune evasion of wild-type (wt) rabies virus (RABV) has been attributed to its glycoprotein (G), particularly to their inefficiency to bind/enter into dendritic cells (DCs). However, the domain responsible for G-mediated DC activation is not clear. In the present study, attempts were made to map the domain(s) on the G involved in differential DC activation using laboratory-adapted and wt viruses. Recombinant RABVs with exchange in each of the structural domains such as signal peptide (sp), ectodomain (et), transmembrane domain (tm), cytoplasmic tail (ct) of the G between wt and laboratory-adapted strains were constructed...
February 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28161579/rational-design-and-efficacy-of-a-multi-epitope-recombinant-protein-vaccine-against-foot-and-mouth-disease-virus-serotype-a-in-pigs
#11
Yimei Cao, Dong Li, Yuanfang Fu, Qifeng Bai, Yingli Chen, Xingwen Bai, Zhizhong Jing, Pu Sun, Huifang Bao, Pinghua Li, Jing Zhang, Xueqing Ma, Zengjun Lu, Zaixin Liu
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and outbreaks of this disease are often economically catastrophic. Recently, a series of outbreaks of foot-and-mouth disease virus (FMDV) serotype A occurred in many countries, including China. Therefore, it is necessary to develop safe and effective vaccines. We designed multi-epitope recombinant proteins A6, A7, and A8 with different three-dimensional structures and compared their immunogenicity in pigs. The results indicated that A8 conferred the greatest protection against FMDV serotype A challenge in pigs, and A8 was selected as the vaccine antigen...
February 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28161578/consensus-m2e-peptide-conjugated-to-gold-nanoparticles-confers-protection-against-h1n1-h3n2-and-h5n1-influenza-a-viruses
#12
Wenqian Tao, Brett Hurst, Akhilesh K Shakya, Md Jasim Uddin, Rohan S Ingrole, Mayra Hernandez-Sanabria, Ravi Arya, Lynn Bimler, Silke Paust, E Bart Tarbet, Harvinder Singh Gill
The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e + sCpG). We demonstrate that intranasal delivery of AuNP-M2e + sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes...
February 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28137624/incorporation-of-a-bi-functional-protein-fimh-enhances-the-immunoprotection-of-chitosan-pvp1-vaccine-against-coxsackievirus-b3-induced-myocarditis
#13
Xiangmei Fan, Yan Yue, Sidong Xiong
Viral myocarditis is a common clinical cardiovascular disease mainly induced by coxsackievirus B3 (CVB3) with no effective therapeutic measures. Induction of efficient mucosal immune responses is very critical against CVB3-induced myocarditis. FimH is an Escherichia coli (E. coli)-derived protein, which possesses an M cell-targeting property and functions as a TLR4 agonist. In this study, we introduced the recombinant FimH protein, into our previously developed CVB3 mucosal vaccine chitosan (CS)-pVP1, aiming to provoke more efficient mucosal immune responses and immunoprotection against CVB3-induced myocarditis...
January 28, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28137623/antiviral-activity-of-ovine-interferon-tau-4-against-foot-and-mouth-disease-virus
#14
Jayaramaiah Usharani, Sun Young Park, Eun-Ju Cho, Chungsu Kim, Young-Joon Ko, Dongseob Tark, Su-Mi Kim, Jong-Hyeon Park, Kwang-Nyeong Lee, Myoung-Heon Lee, Hyang-Sim Lee
Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication...
January 27, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28132867/antiviral-response-and-resistance-analysis-of-treatment-na%C3%A3-ve-hcv-infected-patients-receiving-multiple-doses-of-the-ns3-protease-inhibitor-gs-9256
#15
Hongmei Mo, Charlotte Hedskog, Eric Lawitz, Diana M Brainard, Jenny Yang, William Delaney, Angela Worth, Michael D Miller
The NS3 protease inhibitor (PI) GS-9256 has demonstrated antiviral activity in a monotherapy study and in combination with other DAAs for treatment of chronic hepatitis C virus (HCV) infection. The resistance profile of GS-9256 was investigated in a phase 1 monotherapy study of patients with HCV genotype (GT) 1 infection. No PI resistance associated substitutions (RASs) at positions 36, 155, 156, 168 and 170 were observed at baseline by population sequencing (15% cutoff) in the 54 patients enrolled in the study, however the PI RAS Q80K were detected in 41% of patients at baseline...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28132866/antiviral-prophylaxis-for-preventing-herpes-zoster-in-hematopoietic-stem-cell-transplant-recipients-a-systematic-review-and-meta-analysis
#16
REVIEW
Hyun-Min Seo, Yoon Seob Kim, Chul Hwan Bang, Ji Hyun Lee, Jun Young Lee, Dong-Gun Lee, Young Min Park
The optimal duration of prophylaxis for the varicella-zoster virus following hematopoietic stem cell transplantation (HSCT) remains unclear. The purpose of this study was to systematically review the available literature to determine the optimal duration of antiviral prophylaxis for preventing herpes zoster (HZ) in allogeneic and autologous HSCT recipients. The MEDLINE and EMBASE databases were searched to identify relevant studies. The relative risk (RR) of HZ was calculated using fixed effects or random effects models depending on heterogeneity across the included studies...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28132865/implementation-of-a-non-human-primate-model-of-ebola-disease-infection-of-mauritian-cynomolgus-macaques-and-analysis-of-virus-populations
#17
Géraldine Piorkowski, Frédéric Jacquot, Gilles Quérat, Caroline Carbonnelle, Delphine Pannetier, France Mentré, Hervé Raoul, Xavier de Lamballerie
Ebola virus (EBOV) haemorrhagic fever remains a threat to global public health with an urgent need for an effective treatment. In order to achieve these goals, access to non-human primate (NHP) laboratory models is an essential requirement. Here, we present the first NHP-EBOV laboratory model readily available to the European scientific community, based on infection of Mauritian cynomolgus macaques using a Central-African EBOV strain and increasing virus challenge dose (10, 100, or 1000 focus forming units per animal)...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28131805/tenofovir-alafenamide-taf-does-not-deplete-mitochondrial-dna-in-human-t-cell-lines-at-intracellular-concentrations-exceeding-clinically-relevant-drug-exposures
#18
Kirsten M Stray, Yeojin Park, Darius Babusis, Christian Callebaut, Tomas Cihlar, Adrian S Ray, Michel Perron
HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28131804/downregulation-of-autophagy-related-gene-atg5-and-gabarap-expression-by-ifn-%C3%AE-1-contributes-to-its-anti-hcv-activity-in-human-hepatoma-cells
#19
Xu Li, Yu Li, Shoucai Fang, Jinming Su, Junjun Jiang, Bingyu Liang, Jiegang Huang, Bo Zhou, Ning Zang, Wenzhe Ho, Jieliang Li, Yiping Li, Hui Chen, Li Ye, Hao Liang
Type-III interferon (IFN-λ), the most recently discovered family of IFNs, shares common features with type I IFNs, but also has many distinctive activities. It is not clear that whether IFN-λ has additional antiviral mechanisms. In this study, we investigated the effects of IFN-λ on autophagy, a cellular process closely related to hepatitis C virus (HCV) infection in human hepatoma Huh7 cells. Our results showed that IFN-λ1 treatment inhibit autophagic activity in Huh7 cells, as evidenced by the decreased expression of microtubule-associated protein 1 light chain 3B (LC3B)-II and conversion of LC3B-I to LC3B-II, decreased formation of GFP-LC3 puncta and accumulation of autophagosomes...
January 26, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28115196/oxymatrine-provides-protection-against-coxsackievirus-b3-induced-myocarditis-in-balb-c-mice
#20
Yan Jiang, Yanxin Zhu, Qiuju Mu, Hong Luo, Yan Zhi, Xiangchun Shen
Oxymatrine is the primary pharmacological component of Sophora flavescens Ait. In the present study, we investigated the protective effect of oxymatrine against Coxsackievirus B3-induced myocarditis in mice. Coxsackievirus B3-infected HeLa cells were treated with oxymatrine and the viral titer, as well as the degree of cellular proliferation were determined. Additionally, BALB/c mice were infected with Coxsackievirus B3 and received differing concentrations of oxymatrine. On days 5 and 12 following treatment, mice were sacrificed, and serum lactate dehydrogenase, creatine kinase-MB isozyme, and tumor necrosis factor-α levels were quantified...
January 20, 2017: Antiviral Research
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