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Antiviral Research

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https://www.readbyqxmd.com/read/27919709/evaluation-of-anti-zika-virus-activities-of-broad-spectrum-antivirals-and-nih-clinical-collection-compounds-using-a-cell-based-high-throughput-screen-assay
#1
Robert S Adcock, Yong-Kyu Chu, Jennifer E Golden, Dong-Hoon Chung
Recent studies have clearly underscored the association between Zika virus (ZIKV) and severe neurological diseases such as microcephaly and Guillain-Barre syndrome. Given the historical complacency surrounding this virus, however, no significant antiviral screenings have been performed to specifically target ZIKV. As a result, there is an urgent need for a validated screening method and strategy that is focused on highlighting potential anti-ZIKV inhibitors that can be further advanced via rigorous validation and optimization...
December 2, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27914937/mcl-1-small-molecule-inhibitors-encapsulated-into-nanoparticles-exhibit-increased-killing-efficacy-towards-hcmv-infected-monocytes
#2
Christine M Burrer, Helen Auburn, Xu Wang, Juntao Luo, Fardokht A Abulwerdi, Zaneta Nikolovska-Coleska, Gary C Chan
Human cytomegalovirus (HCMV) spreads and establishes a persistent infection within a host by stimulating the survival of carrier myeloid cells via the upregulation of Mcl-1, an antiapoptotic member of the Bcl-2 family of proteins. However, the lack of potent Mcl-1-specific inhibitors and a targetable delivery system has limited to ability to exploit Mcl-1 as a therapeutic strategy to eliminate HCMV-infected monocytes. In this study, we found a lead compound from a novel class of Mcl-1 small-molecule inhibitors rapidly induced death of HCMV-infected monocytes...
November 30, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908832/evaluation-of-two-strains-of-marek-s-disease-virus-serotype-1-for-the-development-of-recombinant-vaccines-against-very-virulent-infectious-bursal-disease-virus
#3
Kai Li, Yongzhen Liu, Changjun Liu, Li Gao, Yulong Gao, Yanping Zhang, Hongyu Cui, Xiaole Qi, Li Zhong, Xiaomei Wang
Attenuated strains of Marek's disease virus serotype 1 (MDV1), and the closely related herpesvirus of turkeys, are among the most potent vectors for development of recombinant vaccines for poultry. To investigate the effects of MDV1 strain characteristics on the protective efficacy of the recombinant vaccines, we developed two recombinant MDV1 vaccines for expressing the VP2 gene of infectious bursal disease virus (IBDV) based on two different MDV1 strains, the attenuated strain 814 and the Meq gene-deleted recombinant MDV1 strain rLMS△Meq, as the viral vectors...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908831/eukaryotic-translational-initiation-factor-4aii-reduces-the-replication-of-infectious-bursal-disease-virus-by-inhibiting-vp1-polymerase-activity
#4
Li Gao, Kai Li, Li Zhong, Lizhou Zhang, Xiaole Qi, Yongqiang Wang, Yulong Gao, Xiaomei Wang
Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although an interaction between eukaryotic translational initiation factor 4AII (eIF4AII) of the host and viral protein 1 (VP1), the RNA-dependent RNA polymerase (RdRp) of IBDV, has been established, the underlying effects of this interaction on IBDV and the molecular mechanism remain unclear. We here report that interaction of the host eIF4AII with VP1 inhibits the RNA polymerase activity of IBDV to reduce its replication in host cells...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908830/protective-efficacy-of-fc-targeting-conserved-influenza-virus-m2e-antigen-expressed-by-lactobacillus-plantarum
#5
Wen-Tao Yang, Gui-Lian Yang, Qian Wang, Hai-Bin Huang, Yan-Long Jiang, Chun-Wei Shi, Jian-Zhong Wang, Ke-Yan Huang, Yu-Bei Jin, Chun-Feng Wang
The influenza A (H1N1) virus is a highly contagious acute respiratory disease affecting pigs and humans. This disease causes severe economic loss in many countries, and developing mucosal vaccines is an efficient strategy to control the influenza virus. The neonatal Fc receptor (FcRn) plays an important role in transferring IgG across polarized epithelial cells. In the present study, an oral vaccine was developed using Lactobacillus plantarum to deliver the internal influenza viral protein M2e fused to an IgG Fc fragment...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908829/exploring-the-binding-mechanism-of-heteroaryldihydropyrimidines-and-hepatitis-b-virus-capsid-combined-3d-qsar-and-molecular-dynamics
#6
Jing Tu, Jiao Jiao Li, Zhi Jie Shan, Hong Lin Zhai
The non-nucleoside drugs have been developed to treat HBV infection owing to their increased efficacy and lesser side effects, in which heteroaryldihydropyrimidines (HAPs) have been identified as effective inhibitors of HBV capsid. In this paper, the binding mechanism of HAPs targeting on HBV capsid protein was explored through three-dimensional quantitative structure-activity relationship, molecular dynamics and binding free energy decompositions. The obtained models of comparative molecular field analysis and comparative molecular similarity indices analysis enable the sufficient interpretation of structure-activity relationship of HAPs-HBV...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908828/assessment-of-the-potential-for-host-targeted-iminosugars-uv-4-and-uv-5-activity-against-filovirus-infections-in-vitro-and-in-vivo
#7
Kelly L Warfield, Travis K Warren, Xiangguo Qiu, Jay Wells, Chad E Mire, Joan B Geisbert, Kelly S Stuthman, Nicole L Garza, Sean A Van Tongeren, Amy C Shurtleff, Krystle N Agans, Gary Wong, Michael V Callahan, Thomas W Geisbert, Brennan Klose, Urban Ramstedt, Anthony M Treston
Iminosugars are host-directed antivirals with broad-spectrum activity. The iminosugar, N-butyl-deoxynojirimycin (NB-DNJ or Miglustat(®)), is used in humans for treatment of Gaucher's disease and has mild antiviral properties. More potent analogs of NB-DNJ have been generated and have demonstrated activity against a variety of viruses including flaviviruses, influenza, herpesviruses and filoviruses. In the current study, a panel of analogs based on NB-DNJ was analyzed for activity against Ebola (EBOV) and Marburg viruses (MARV)...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908827/different-routes-and-doses-influence-protection-in-pigs-immunised-with-the-naturally-attenuated-african-swine-fever-virus-isolate-ourt88-3
#8
Pedro J Sánchez-Cordón, Dave Chapman, Tamara Jabbar, Ana L Reis, Lynnette Goatley, Christopher L Netherton, Geraldine Taylor, Maria Montoya, Linda Dixon
This study compares different combinations of doses and routes of immunisation of pigs with low virulent African swine fever virus (ASFV) genotype I isolate OURT88/3, including the intramuscular and intranasal route, the latter not previously tested. Intranasal immunisations with low and moderate doses (10(3) and 10(4) TCID50) of OURT88/3 provided complete protection (100%) against challenge with virulent genotype I OURT88/1 isolate. Only mild and transient clinical reactions were observed in protected pigs...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902933/the-fda-approved-drug-sofosbuvir-inhibits-zika-virus-infection
#9
Kristen M Bullard-Feibelman, Jennifer Govero, Zhe Zhu, Vanessa Salazar, Milena Veselinovic, Michael S Diamond, Brian J Geiss
The rapidly expanding Zika virus (ZIKV) epidemic has affected thousands of individuals with severe cases causing Guillain-Barré syndrome, congenital malformations, and microcephaly. Currently, there is no available vaccine or therapy to prevent or treat ZIKV infection. We evaluated whether sofosbuvir, an FDA-approved nucleotide polymerase inhibitor for the distantly related hepatitis C virus, could have antiviral activity against ZIKV infection. Cell culture studies established that sofosbuvir efficiently inhibits replication and infection of several ZIKV strains in multiple human tumor cell lines and isolated human fetal-derived neuronal stem cells...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902932/adenosine-triphosphate-analogs-can-efficiently-inhibit-the-zika-virus-rna-dependent-rna-polymerase
#10
Kamil Hercík, Jaroslav Kozak, Michal Šála, Milan Dejmek, Hubert Hřebabecký, Eva Zborníková, Miroslav Smola, Daniel Ruzek, Radim Nencka, Evzen Boura
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27890675/synergistic-drug-combination-effectively-blocks-ebola-virus-infection
#11
Wei Sun, Shihua He, Carles Martínez-Romero, Jennifer Kouznetsova, Gregory Tawa, Miao Xu, Paul Shinn, Ethan Fisher, Yan Long, Omid Motabar, Shu Yang, Philip E Sanderson, Peter R Williamson, Adolfo García-Sastre, Xiangguo Qiu, Wei Zheng
Although a group of FDA-approved drugs were previously identified with activity against Ebola virus, most of them are not clinically useful because their human blood concentrations are not high enough to inhibit EBOV infection. We screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of three-drug combinations, toremifene-mefloquine-posaconazole and toremifene-clarithromycin-posaconazole, were identified that effectively blocked EBOV entry and were further validated for inhibition of live EBOV infection...
November 24, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27890674/passive-immunotherapy-for-middle-east-respiratory-syndrome-coronavirus-infection-with-equine-immunoglobulin-or-immunoglobulin-fragments-in-a-mouse-model
#12
Yongkun Zhao, Chong Wang, Boning Qiu, Chufang Li, Hualei Wang, Hongli Jin, Weiwei Gai, Xuexing Zheng, Tiecheng Wang, Weiyang Sun, Feihu Yan, Yuwei Gao, Qian Wang, Jinghua Yan, Ling Chen, Stanley Perlman, Nanshan Zhong, Jincun Zhao, Songtao Yang, Xianzhu Xia
Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection caused by a coronavirus (CoV), MERS-CoV. With the continuing spread of MERS-CoV, prophylactic and therapeutic treatments are urgently needed. In this study, we prepared purified equine F(ab')2 from horses immunized with MERS-CoV virus-like particles (VLPs) expressing MERS-CoV S, M and E proteins. Both IgG and F(ab')2 efficiently neutralized MERS-CoV replication in tissue culture. Passive transfer of equine immune antibodies significantly reduced virus titers and accelerated virus clearance from the lungs of MERS-CoV infected mice...
November 24, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27889530/identification-of-proximal-biomarkers-of-pkc-agonism-and-evaluation-of-their-role-in-hiv-reactivation
#13
Sai Vikram Vemula, Jill W Maxwell, Alexey Nefedov, Bang-Lin Wan, Justin Steve, William Newhard, Rosa I Sanchez, David Tellers, Richard J Barnard, Wade Blair, Daria Hazuda, Andrea L Webber, Bonnie J Howell
DESIGN: The HIV latent CD4(+) T cell reservoir is broadly recognized as a barrier to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is one approach under investigation for reactivation of latently infected CD4(+) T cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and Dandekar, 2015). We proposed that an increased understanding of the molecular mechanisms of action of PKC agonists was necessary to inform on biological signaling and pharmacodynamic biomarkers...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27889529/antiviral-activities-of-selected-antimalarials-against-dengue-virus-type-2-and-zika-virus
#14
Anuradha Balasubramanian, Tadahisa Teramoto, Amol A Kulkarni, Apurba K Bhattacharjee, Radhakrishnan Padmanabhan
In a previous study, twelve antimalarial compounds, amodiaquine (AQ) and derivatives, were shown to have potent anti-dengue viral (DENV) activity by using the stable DENV2 Renilla luciferase reporter replicon expressing BHK-21 cells, infectivity (plaque), and the qRT-PCR assays. In this study, we performed molecular modeling on these compounds to determine their stereo-electronic properties required for optimal antiviral activity. Based on the similarity of calculated stereo-electronic profiles, specifically the electrostatic potential profiles of the compounds, and in silico screening of related compounds from literature, we identified three additional compounds, Quinacrine (QC), Mefloquine (MQ), and GSK369796...
November 23, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27887982/genotypic-resistance-of-cytomegalovirus-to-antivirals-in-hematopoietic-stem-cell-transplant-recipients-from-portugal-a-retrospective-study
#15
Ana Bela Campos, Joana Ribeiro, Carlos Pinho Vaz, Fernando Campilho, Rosa Branca, António Campos, Inês Baldaque, Rui Medeiros, David Boutolleau, Hugo Sousa
The aim of this study was to characterize Human Cytomegalovirus (HCMV) drug resistance mutations in UL97 and UL54 genes in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients in Portugal. We have performed a retrospective study with 22 patients from a cohort of patients with different haematological malignancies submitted to allo-HSCT between 2010 and 2014. Patients were selected according to clinical and laboratory data of HCMV infection and management. HCMV resistance mutations were characterized by sequencing of UL97 and UL54 genes...
November 22, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27876497/hepatitis-c-virus-inhibits-cd4-t-cell-function-via-binding-to-toll-like-receptor-7
#16
Dalila Mele, Stefania Mantovani, Barbara Oliviero, Giulia Grossi, Serena Ludovisi, Mario U Mondelli, Stefania Varchetta
Toll-like receptor 7 (TLR7) is a ssRNA receptor that activates dendritic cells and macrophages upon ssRNA binding; however, little is known of its role in CD4(+) T cells. We show here that hepatitis C virus (HCV) induces a dose dependent inhibition of cytokine production and expression of activation markers in CD4 T cells, which were restored by a TLR7-specific antagonist. These findings indicate that HCV induces CD4 T cell impairment via TLR7 which may contribute to failure of virus eradication, casting doubts on the use of TLR7 agonists to boost innate immunity in chronic RNA virus infections...
November 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27871886/tetrahalogenated-benzimidazole-d-ribonucleosides-are-active-against-rat-cytomegalovirus
#17
Alexandra Dittmer, Ina Woskobojnik, Rebekka Adfeldt, John C Drach, Leroy B Townsend, Sebastian Voigt, Elke Bogner
BACKGROUND: Benzimidazole D-ribonucleosides are potent and selective inhibitors of CMV infection that have been shown to target the viral terminase, the enzyme complex responsible for viral DNA cleavage into single unit-length genomes and subsequent DNA packaging into procapsids. Here, we evaluated the viral inhibition by benzimidazole D-ribonucleosides against rat cytomegalovirus (RCMV). METHODS: Antiviral activity of compounds Cl4RB and BTCRB against RCMV was quantified by measurement of plaque formation...
November 18, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27864075/the-natural-compound-silvestrol-is-a-potent-inhibitor-of-ebola-virus-replication
#18
Nadine Biedenkopf, Kerstin Lange-Grünweller, Falk W Schulte, Aileen Weißer, Christin Müller, Dirk Becker, Stephan Becker, Roland K Hartmann, Arnold Grünweller
The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation initiation complex in eukaryotes, is an important novel drug target in cancer research because its helicase activity is required to unwind extended and highly structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound isolated from the plant Aglaia foveolata, is a highly efficient, non-toxic and specific inhibitor of eIF4A. Importantly, 5'-capped viral mRNAs often contain structured 5'-UTRs as well, which may suggest a dependence on eIF4A for their translation by the host protein synthesis machinery...
November 15, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27864074/clinically-isolated-enterovirus-a71-subgenogroup-c4-strain-with-lethal-pathogenicity-in-14-day-old-mice-and-the-application-as-an-ev-a71-mouse-infection-model
#19
Yi Xu, Shuzhi Ma, Limeng Zhu, Zhiqiu Huang, Liyun Chen, Yuhua Xu, Haibin Yin, Tao Peng, Yi Wang
The Enterovirus A71 (EV-A71) subgenogroup C4 is prevalent in China. EV-A71 causes hand, foot and mouth disease (HFMD) in children and may lead to severe neurological diseases. The development of antiviral and protective vaccines against EV-A71 is significantly hindered by the lack of suitable animal models to recapitulate human neurological symptoms. In this study, GZ-CII, a highly virulent EV-A71 subgenogroup C4 strain, was isolated from hospitalized children with HFMD. Intraperitoneal infections of GZ-CII resulted in progressive neurological disease in mice as old as 14 days...
November 15, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27847245/celastrol-inhibits-dengue-virus-replication-via-up-regulating-type-i-interferon-and-downstream-interferon-stimulated-responses
#20
Jung-Sheng Yu, Chin-Kai Tseng, Chun-Kuang Lin, Yao-Chin Hsu, Yu-Hsuan Wu, Ching-Liang Hsieh, Jin-Ching Lee
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported...
November 12, 2016: Antiviral Research
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