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Antiviral Research

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https://www.readbyqxmd.com/read/29782877/analysis-of-spontaneous-resolution-of-cytomegalovirus-replication-after-transplantation-in-cmv-seropositive-patients-with-pretransplant-cd8-ifng-response
#1
Aurora Páez-Vega, Antonio Poyato, Alberto Rodriguez-Benot, Lluis Guirado, Jesús Fortún, Oscar Len, Edson Abdala, María C Fariñas, Elisa Cordero, Carmen de Gracia, Domingo Hernández, Rafael González, Julián Torre-Cisneros, Sara Cantisán
This prospective study evaluates whether CMV-seropositive (R+) transplant patients with pretransplant CD8+IFNG+ T-cell response to cytomegalovirus (CMV) (CD8+IFNG+ response) can spontaneously clear the CMV viral load without requiring treatment. A total of 104 transplant patients (kidney/liver) with pretransplant CD8+IFNG+ response were evaluable. This response was determined using QuantiFERON-CMV assay. The incidence of CMV replication and disease was 45.2% (47/104) and 6.7% (7/104), respectively. Of the total patients, 77...
May 18, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29758235/innovation-and-trends-in-the-development-and-approval-of-antiviral-medicines-1987-2017-and-beyond
#2
REVIEW
Shuvam Chaudhuri, Julian A Symons, Jerome Deval
2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV infection. Here, we provide a retrospective analysis of approved antiviral drugs, including therapeutics against other major chronic infections such as hepatitis B and C, and herpes viruses, over the last thirty years. During this time, only a few drugs were approved to treat acute viral infections, mainly influenza...
May 15, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29772254/effect-of-interferon-alpha-and-cyclosporine-treatment-separately-and-in-combination-on-middle-east-respiratory-syndrome-coronavirus-mers-cov-replication-in-a-human-in-vitro-and-ex-vivo-culture-model
#3
H S Li, Denise I T Kuok, M C Cheung, Mandy M T Ng, K C Ng, Kenrie P Y Hui, J S Malik Peiris, Michael C W Chan, John M Nicholls
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication...
May 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29758236/identification-of-compound-b-a-novel-anti-dengue-virus-agent-targeting-the-non-structural-protein-4a
#4
Haruaki Nobori, Shinsuke Toba, Ryu Yoshida, William W Hall, Yasuko Orba, Hirofumi Sawa, Akihiko Sato
No abstract text is available yet for this article.
May 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29753658/feasibility-and-biological-rationale-of-repurposing-sunitinib-and-erlotinib-for-dengue-treatment
#5
Szuyuan Pu, Fei Xiao, Stanford Schor, Elena Bekerman, Fabio Zanini, Rina Barouch-Bentov, Claude M Nagamine, Shirit Einav
There is an urgent need for strategies to combat dengue virus (DENV) infection; a major global threat. We reported that the cellular kinases AAK1 and GAK regulate intracellular trafficking of multiple viruses and that sunitinib and erlotinib, approved anticancer drugs with potent activity against these kinases, protect DENV-infected mice from mortality. Nevertheless, further characterization of the therapeutic potential and underlying mechanism of this approach is required prior to clinical evaluation. Here, we demonstrate that sunitinib/erlotinib combination achieves sustained suppression of systemic infection at approved dose in DENV-infected IFN-α/β and IFN-γ receptor-deficient mice...
May 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29753657/irf-1-rig-i-and-mda5-display-potent-antiviral-activities-against-norovirus-coordinately-induced-by-different-types-of-interferons
#6
Wen Dang, Lei Xu, Yuebang Yin, Sunrui Chen, Wenshi Wang, Mohamad S Hakim, Kyeong-Ok Chang, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus represents the main cause of acute nonbacterial gastroenteritis worldwide. In immunocompromised patients, it bears high risk of causing chronic infection with significant morbidity and mortality. The lack of specific treatment prompts the development of anti-norovirus agents. In this study, we have investigated the role of interferon (IFN) response and evaluated antiviral activities of different IFNs against human norovirus (HuNoV) replication using a HuNoV replicon model. We found that HuNoV RNA replication was sensitive to all types of IFNs, including IFNα (type I), IFNγ (type II), IFNλ1 and 3 (type III)...
May 10, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29752950/minocycline-suppresses-dengue-virus-replication-by-down-regulation-of-macrophage-migration-inhibitory-factor-induced-autophagy
#7
Yen-Chung Lai, Yung-Chun Chuang, Chih-Peng Chang, Yee-Shin Lin, Guey-Chuen Perng, Han-Chung Wu, Shie-Liang Hsieh, Trai-Ming Yeh
Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection of which there is no licensed therapeutic drug available. Previous studies have shown that minocycline, an antibiotic, can inhibit DENV infection in vitro. However, the mechanism is not fully understood. It is known that macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in dengue disease development; MIF can induce autophagy, and autophagy can facilitate DENV replication. Therefore, we tested the hypothesis that MIF-induced autophagy is involved in minocycline treatment against DENV infection...
May 9, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29709564/peptides-p4-and-p7-derived-from-e-protein-inhibit-entry-of-dengue-virus-serotype-2-via-interacting-with-%C3%AE-3-integrin
#8
Xiaoyun Cui, Yanhua Wu, Dongying Fan, Na Gao, Ying Ming, Peigang Wang, Jing An
Dengue virus (DENV) infection has become a severe public health problem worldwide. However, there is no specific antiviral drug available yet. In this study, we found that DENV serotype 2 (DENV2) infection enhanced the expression of β3 integrin on human umbilical vein endothelial cells (HUVECs) and that DENV2 antigens co-localized with β3 integrin. DENV2 envelope protein (E) directly interacted with β3 integrin, and their interacting sites were located at domain III of E protein (EDIII). Several synthetic peptides were designed based on the amino acid sequence of EDIII, and peptides P4 and P7 could inhibit DENV2 entry into HUVECs in a dose-dependent manner...
April 27, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29709563/characterization-and-structure-activity-relationship-analysis-of-a-class-of-antiviral-compounds-that-directly-bind-dengue-virus-capsid-protein-and-are-incorporated-into-virions
#9
Jessica L Smith, Kayla Sheridan, Christopher J Parkins, Lisa Frueh, Adriana L Jemison, Kathleya Strode, Geoffrey Dow, Aaron Nilsen, Alec J Hirsch
Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions and cause significant morbidity and mortality worldwide. Although a partially effective vaccine is in use in several countries in which DENV are endemic, no antiviral therapeutics are approved for combating DENV-associated disease. Herein, we report the characterization of novel small molecule inhibitors of DENV replication, VGTI-A3 and VGTI-A3-03, as well as structure-activity relationship analysis of the molecules using a panel of chemical analogs...
April 27, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29709562/novel-cyclo-peptides-inhibit-ebola-pseudotyped-virus-entry-by-targeting-primed-gp-protein
#10
Quanjie Li, Ling Ma, Dongrong Yi, Han Wang, Jing Wang, Yongxin Zhang, Ying Guo, Xiaoyu Li, Jinming Zhou, Yi Shi, George F Gao, Shan Cen
Ebola virus (EBOV) causes fatal hemorrhagic fever with high death rates in human. Currently, there are no available clinically-approved prophylactic or therapeutic treatments. The recently solved crystal structure of cleavage-primed EBOV glycoprotein (GPcl) in complex with the C domain of endosomal protein Niemann-Pick C1 (NPC1) provides a new target for the development of EBOV entry inhibitors. In this work, a computational approach using docking and molecular dynamic simulations is carried out for the rational design of peptide inhibitors...
April 27, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29702120/chinese-herbal-extract-su-duxing-had-potent-inhibitory-effects-on-both-wild-type-and-entecavir-resistant-hepatitis-b-virus-hbv-in-vitro-and-effectively-suppressed-hbv-replication-in-mouse-model
#11
Yan Liu, Weiming Yao, Lanlan Si, Jun Hou, Jiabo Wang, Zhihui Xu, Weijie Li, Jianhong Chen, Ruisheng Li, Penggao Li, Lvping Bo, Xiaohe Xiao, Jinchu Lan, Dongping Xu
The present study aimed to investigate anti-HBV effect and major active compounds of Su-duxing, a medicine extracted from Chinese herbs. HBV-replicating cell lines HepG2.2.15 (wild-type) and HepG2. A64 (entecavir-resistant) were used for in vitro test. C57BL/6 mice infected by adeno-associated virus carrying 1.3 mer wild-type HBV genome were used for in vivo test. Inhibitory rates of Su-duxing (10 μg/mL) on HBV replicative intermediate and HBsAg levels were 75.1%, 51.0% in HepG2.2.15 cells and 65.2%, 42...
April 24, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29698664/novel-activities-of-safe-in-human-broad-spectrum-antiviral-agents
#12
Aleksandr Ianevski, Eva Zusinaite, Suvi Kuivanen, Mårten Strand, Hilde Lysvand, Mona Teppor, Laura Kakkola, Henrik Paavilainen, Mira Laajala, Hannimari Kallio-Kokko, Miia Valkonen, Anu Kantele, Kaidi Telling, Irja Lutsar, Pille Letjuka, Natalja Metelitsa, Valentyn Oksenych, Magnar Bjørås, Svein Arne Nordbø, Uga Dumpis, Astra Vitkauskiene, Christina Öhrmalm, Kåre Bondeson, Anders Bergqvist, Tero Aittokallio, Rebecca J Cox, Magnus Evander, Veijo Hukkanen, Varpu Marjomaki, Ilkka Julkunen, Olli Vapalahti, Tanel Tenson, Andres Merits, Denis Kainov
According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus...
April 23, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29680670/identification-of-small-molecule-inhibitors-of-the-chikungunya-virus-nsp1-rna-capping-enzyme
#13
Kristen M Feibelman, Benjamin P Fuller, Linfeng Li, Daniel V LaBarbera, Brian J Geiss
Chikungunya virus (CHIKV) is an arthropod-borne alphavirus. Alphaviruses are positive strand RNA viruses that require a 5' cap structure to direct translation of the viral polyprotein and prevent degradation of the viral RNA genome by host cell nucleases. Formation of the 5' RNA cap is orchestrated by the viral protein nsP1, which binds GTP and provides the N-7 methyltransferase and guanylyltransferase activities that are necessary for cap formation. Viruses with aberrant nsP1 activity are unable to replicate effectively suggesting that nsP1 is a promising target for antiviral drug discovery...
April 20, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29678552/the-immunogenicity-of-recombinant-vaccines-based-on-modified-vaccinia-ankara-mva-viruses-expressing-african-horse-sickness-virus-vp2-antigens-depends-on-the-levels-of-expressed-vp2-protein-delivered-to-the-host
#14
Eva Calvo-Pinilla, Simon Gubbins, Peter Mertens, Javier Ortego, Javier Castillo-Olivares
African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV. Attenuated vaccines for AHS are considered unsuitable for use in non-endemic countries due bio-safety concerns...
April 17, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29678551/anti-respiratory-syncytial-virus-rsv-g-monoclonal-antibodies-reduce-lung-inflammation-and-viral-lung-titers-when-delivered-therapeutically-in-a-balb-c-mouse-model
#15
Hayat Caidi, Congrong Miao, Natalie J Thornburg, Ralph A Tripp, Larry J Anderson, Lia M Haynes
RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab)...
April 17, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29674164/impact-of-r152k-and-r368k-neuraminidase-catalytic-substitutions-on-in-vitro-properties-and-virulence-of-recombinant-a-h1n1-pdm09-viruses
#16
Véronique Tu, Yacine Abed, Clément Fage, Mariana Baz, Guy Boivin
Neuraminidase (NA) mutations conferring resistance to NA inhibitors (NAIs) are expected to occur at framework or catalytic residues of the NA enzyme. Numerous clinical and in vitro reports already described NAI-resistant A(H1N1)pdm09 variants harboring various framework NA substitutions. By contrast, variants with NA catalytic changes remain poorly documented. Herein, we investigated the effect of R152K and R368K NA catalytic mutations on the NA enzyme properties, in vitro replicative capacity and virulence of A(H1N1)pdm09 recombinant viruses...
April 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29665376/insect-cell-produced-recombinant-protein-subunit-vaccines-protect-against-zika-virus-infection
#17
Panke Qu, Wei Zhang, Dapeng Li, Chao Zhang, Qingwei Liu, Xueyang Zhang, Xuesong Wang, Wenlong Dai, Yongfen Xu, Qibin Leng, Jin Zhong, Xia Jin, Zhong Huang
Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29665375/luteolin-escape-mutants-of-dengue-virus-map-to-prm-and-ns2b-and-reveal-viral-plasticity-during-maturation
#18
Minhua Peng, Crystall Marie Dawn Swarbrick, Kitti Wing-Ki Chan, Dahai Luo, Wei Zhang, Xiaoping Lai, Geng Li, Subhash G Vasudevan
We previously showed that luteolin, a well-known plant-derived component found in the "heat clearing" class of Traditional Chinese Medicine (TCM) herbs, is an uncompetitive inhibitor (Ki 58.6 μM) of the host proprotein convertase furin, an endoprotease that is required for maturation of flaviviruses in the trans-Golgi compartment. Luteolin also weakly inhibited recombinant dengue virus NS2B/NS3 protease (Ki 140.36 μM) non-competitively. In order to further explore the mechanism of inhibition we isolated resistant mutants by continuous passaging of DENV2 in the presence of increasing concentrations of luteolin...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29665374/spectrum-of-activity-testing-for-therapeutics-against-all-four-dengue-virus-serotypes-in-ag129-mouse-models-proof-of-concept-studies-with-the-adenosine-nucleoside-inhibitor-nitd-008
#19
Gregg N Milligan, Mellodee White, Diana Zavala, Richard B Pyles, Vanessa V Sarathy, Alan D T Barrett, Nigel Bourne
Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29665373/human-monoclonal-antibodies-against-west-nile-virus-from-japanese-encephalitis-vaccinated-volunteers
#20
Tatsuhiko Ozawa, Hideyuki Masaki, Tomohiko Takasaki, Ikuko Aoyama, Takahiro Yumisashi, Atsushi Yamanaka, Eiji Konishi, Yoh Ohnuki, Atsushi Muraguchi, Hiroyuki Kishi
West Nile virus (WNV) is a positive-sense single-stranded RNA flavivirus belonging to the Japanese encephalitis virus (JEV) serocomplex of the Flaviviridae family and causes mosquito-borne infections. Although most human infection cases are asymptomatic, approximately one in 150 infected individuals develops meningoencephalitis, with a mortality rate of 4-14%. While the development of human neutralizing antibody therapeutics against WNV is strongly anticipated, WNV is difficult to study in conventional laboratories due to its high safety level requirement...
April 14, 2018: Antiviral Research
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