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Antiviral Research

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https://www.readbyqxmd.com/read/28712942/structure-based-discovery-of-clinically-approved-drugs-as-zika-virus-ns2b-ns3-protease-inhibitors-that-potently-inhibit-zika-virus-infection-in-vitro-and-in-vivo
#1
Shuofeng Yuan, Jasper Fuk-Woo Chan, Helena den-Haan, Kenn Ka-Heng Chik, Anna Jinxia Zhang, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Cyril Chik-Yan Yip, Winger Wing-Nga Mak, Zheng Zhu, Zijiao Zou, Kah-Meng Tee, Jian-Piao Cai, Kwok-Hung Chan, Jorge de la Peña, Horacio Pérez-Sánchez, José Pedro Cerón-Carrasco, Kwok-Yung Yuen
Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir)...
July 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28709658/ngago-gdna-system-efficiently-suppresses-hepatitis-b-virus-replication-through-accelerating-decay-of-pregenomic-rna
#2
Zhuanchang Wu, Siyu Tan, Leiqi Xu, Lifen Gao, Haizhen Zhu, Chunhong Ma, Xiaohong Liang
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression...
July 12, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28709657/detection-of-the-hepatitis-b-virus-hbv-covalently-closed-circular-dna-cccdna-in-mice-transduced-with-a-recombinant-aav-hbv-vector
#3
Julie Lucifora, Anna Salvetti, Xavier Marniquet, Laurent Mailly, Barbara Testoni, Floriane Fusil, Aurore Inchauspé, Maud Michelet, Marie-Louise Michel, Massimo Levrero, Pierre Cortez, Thomas F Baumert, François-Loic Cosset, Cécile Challier, Fabien Zoulim, David Durantel
Hepatitis B Virus (HBV) persists in infected hepatocytes as an episomal covalently-closed-circular DNA mini-chromosome, called cccDNA. As the main nuclear transcription template, HBV cccDNA is a key replication intermediate in the viral life cycle. Little is known about the mechanisms involved in its formation, maintenance and fate under antiviral therapies. This is mainly due to the lack of small immune-competent animal models able to recapitulate the entire HBV replication cycle, including formation of HBV cccDNA...
July 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28705625/antiviral-activity-of-gemcitabine-against-human-rhinovirus-in%C3%A2-vitro-and-in%C3%A2-vivo
#4
Jae-Hyoung Song, Seong-Ryeol Kim, Eun-Young Heo, Jae-Young Lee, Dong-Eun Kim, Sungchan Cho, Sun-Young Chang, Byung-Il Yoon, Jeongmin Seong, Hyun-Jeong Ko
Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model...
July 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28698014/adenoviral-expressed-recombinant-granulocyte-monocyte-colony-stimulating-factor-gm-csf-enhances-protective-immunity-induced-by-inactivated-newcastle-disease-virus-ndv-vaccine
#5
Xinglong Wang, Xiangwei Wang, Yanqing Jia, Chongyang Wang, Qinqsong Han, Zen H Lu, Zengqi Yang
Although vaccination has been hugely successful in protecting birds against infection by the New castle disease virus (NDV), newly-emerged highly virulent strains have been found to overcome established immune protection and threaten the poultry industry. The need to improve the immunization efficacy is, therefore, urgent. Here, we tested the potential immunostimulatory adjuvant activity of the adenoviral-expressed recombinant chicken granulocyte monocyte colony stimulating factor (rchGM-CSF) in an inactivated Newcastle Disease Virus (NDV) vaccine...
July 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28690142/identification-of-an-essential-virulence-gene-of-cyprinid-herpesvirus-3
#6
Maxime Boutier, Yuan Gao, Catherine Vancsok, Nicolás M Suárez, Andrew J Davison, Alain Vanderplasschen
The genus Cyprinivirus consists of a growing list of phylogenetically related viruses, some of which cause severe economic losses to the aquaculture industry. The archetypal member, cyprinid herpesvirus 3 (CyHV-3) causes mass mortalities worldwide in koi and common carp. A CyHV-3 mutant was described previously that is attenuated in vivo by a deletion affecting two genes (ORF56 and ORF57). The relative contributions of ORF56 and ORF57 to the safety and efficacy profile of this vaccine candidate have now been assessed by analysing viruses individually deleted for ORF56 or ORF57...
July 6, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28688753/antiviral-effects-of-retro-2-cycl-and-retro-2-1-against-enterovirus-71-in%C3%A2-vitro-and-in%C3%A2-vivo
#7
Wenwen Dai, Yu Wu, Jinpeng Bi, Xiaotong Lu, Ali Hou, Yan Zhou, Bo Sun, Wei Kong, Julien Barbier, Jean-Christophe Cintrat, Feng Gao, Daniel Gillet, Weiheng Su, Chunlai Jiang
Enterovirus 71 (EV71) is one of the causative pathogens of hand, foot and mouth disease (HFMD), especially the form associated with fatal neurological disorders. Sustained outbreaks of EV71 infections remain a serious health threat worldwide. However, no antiviral agent against EV71 for clinical therapy has been approved. Retro-2(cycl) and Retro-2.1 are inhibitors of several pathogens specifically targeting the intracellular vesicle transport, which also participates in the EV71 lifecycle processes including progeny virus release...
July 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28676302/comparison-of-three-dimensional-synergistic-analyses-of-percentage-versus-logarithmic-data-in-antiviral-studies
#8
Donald F Smee, Mark N Prichard
Cell culture antiviral experiments were conducted in order to understand the relationship between percentage data generated by plaque reduction (PR) and logarithmic data derived by virus yield reduction (VYR) assays, using three-dimensional MacSynergy II software. The relationship between percentage and logarithmic data has not been investigated previously. Interpretation of drug-drug interactions is based on a Volume of Synergy (VS) calculation, which can be positive (synergy), negative (antagonistic), or neutral (no or minimal interaction)...
July 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28676301/toward-the-identification-of-viral-cap-methyltransferase-inhibitors-by-fluorescence-screening-assay
#9
Wahiba Aouadi, Cécilia Eydoux, Bruno Coutard, Baptiste Martin, Françoise Debart, Jean Jacques Vasseur, Jean Marie Contreras, Christophe Morice, Gilles Quérat, Marie-Louise Jung, Bruno Canard, Jean-Claude Guillemot, Etienne Decroly
Two highly pathogenic human coronaviruses associated with severe respiratory syndromes emerged since the beginning of the century. The severe acute respiratory syndrome SARS-coronavirus (CoV) spread first in southern China in 2003 with about 8000 infected cases in few months. Then in 2012, the Middle East respiratory syndrome (MERS-CoV) emerged from the Arabian Peninsula giving a still on-going epidemic associated to a high fatality rate. CoVs are thus considered a major health threat. This is especially true as no vaccine nor specific therapeutic are available against either SARS- or MERS-CoV...
July 1, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28673801/novel-peptidyl-%C3%AE-aminoalkylphosphonates-as-inhibitors-of-hepatitis-c-virus-ns3-4a-protease
#10
Marcin Skoreński, Magdalena Pachota, Krzysztof Pyrć, Marcin Sieńczyk, Józef Oleksyszyn
Herein, we describe the synthesis and application of novel phosphonic inhibitors designed to target the NS3/4A protease, which is crucial for the life cycle of hepatitis C virus. We examined the inhibitory potency of our synthesized compounds against two genotypes (1a and 1b) of NS3/4A protease and four mutant strains of HCV. The most potent inhibitors displayed k2/KI values of 79 850 M(-1)s(-1) and 60 850 M(-1)s(-1) against genotype 1a and 1b protease, respectively. Further in vitro evaluation of the most potent inhibitors revealed that vastly reduced HCV replication...
June 30, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28673800/modeling-hcv-cure-after-an-ultra-short-duration-of-therapy-with-direct-acting-agents
#11
Ashish Goyal, Yoav Lurie, Eric G Meissner, Marian Major, Natasha Sansone, Susan L Uprichard, Scott J Cotler, Harel Dahari
BACKGROUND: Cases of sustained-virological response (SVR or cure) after an ultra-short duration (≤27 days) of direct-acting antiviral (DAA)-based therapy, despite HCV being detected at end of treatment (EOT), have been reported. Established HCV mathematical models that predict the treatment duration required to achieve cure do not take into account the possibility that the infectivity of virus produced during treatment might be reduced. The aim of this study was to develop a new mathematical model that considers the fundamental and critical concept that HCV RNA in serum represents both infectious virus (Vi) and non-infectious virus (Vni) in order to explain the observation of cure with ultrashort DAA therapy...
June 30, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28668556/1-2-3-4-6-penta-o-galloyl-%C3%A3-d-glucose-a-bioactive-compound-in-elaeocarpus-sylvestris-extract-inhibits-varicella-zoster-virus-replication
#12
Sohee Bae, Sun Yeou Kim, Moon Ho Do, Chan Hee Lee, Yoon-Jae Song
The aim of this study was to establish the effect of a 70% ethanol extract of Elaeocarpus sylvestris (ESE) on varicella-zoster virus (VZV) replication and identify the specific bioactive component(s) underlying its activity. ESE induced a significant reduction in replication of the clinical strain of VZV. Activity-guided fractionation indicated that the ethyl acetate (EtOAc) fraction of ESE contains the active compound(s) inhibiting VZV replication. High-Performance Liquid Chromatography coupled to Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry (HPLC-Q-TOF-MS/MS) analysis of the EtOAc fraction of ESE facilitated the identification of 13 chemical components...
June 29, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28666757/a-novel-chimeric-hepatitis-b-virus-s-pres1-antigen-produced-in-mammalian-and-plant-cells-elicits-stronger-humoral-and-cellular-immune-response-than-the-standard-vaccine-constituent-s-protein
#13
Mihaela-Olivia Dobrica, Catalin Lazar, Lisa Paruch, Hanne Skomedal, Hege Steen, Sissel Haugslien, Catalin Tucureanu, Iuliana Caras, Adrian Onu, Sonya Ciulean, Alexandru Branzan, Jihong Liu Clarke, Crina Stavaru, Norica Branza-Nichita
Chronic Hepatitis B Virus (HBV) infection leads to severe liver pathogenesis associated with significant morbidity and mortality. As no curable medication is yet available, vaccination remains the most cost-effective approach to limit HBV spreading and control the infection. Although safe and efficient, the standard vaccine based on production of the small (S) envelope protein in yeast fails to elicit an effective immune response in about 10% of vaccinated individuals, which are at risk of infection. One strategy to address this issue is the development of more immunogenic antigens...
June 27, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28647474/antiviral-profiling-of-the-capsid-assembly-modulator-bay41-4109-on-full-length-hbv-genotype-a-h-clinical-isolates-and-core-site-directed-mutants-in%C3%A2-vitro
#14
Jan Martin Berke, Ying Tan, Thierry Verbinnen, Pascale Dehertogh, Karen Vergauwen, Ann Vos, Oliver Lenz, Frederik Pauwels
The HBV core protein represents an attractive target for new antiviral therapies due to its multiple functions within the viral life-cycle. Here, we report the antiviral activity of the capsid assembly modulator (CAM) BAY41-4109 and two nucleos(t)ide analogues (NAs) on a diverse panel of 54 HBV clinical isolates from genotype (GT) A-H and assessed the impact of core amino acid (aa) substitutions using site-directed mutants (SDMs). The median EC50 values of BAY41-4109 across genotypes ranged from 26 nM in GT G to 215 nM in GT F irrespective of the presence of NA resistance mutations compared to 43 nM for the GT D reference construct...
June 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28645623/identification-of-a-coumarin-based-antihistamine-as-an-anti-filoviral-entry-inhibitor
#15
Han Cheng, Adam Schafer, Veronica Soloveva, Dima Gharaibeh, Tara Kenny, Cary Retterer, Rouzbeh Zamani, Sina Bavari, Norton P Peet, Lijun Rong
Filoviruses, consisting of Ebola virus, Marburg virus and Cuevavirus, cause severe hemorrhagic fevers in humans with high mortality rates up to 90%. Currently, there is no approved vaccine or therapy available for the prevention and treatment of filovirus infection in humans. The recent 2013-2015 West African Ebola epidemic underscores the urgency to develop antiviral therapeutics against these infectious diseases. Our previous study showed that GPCR antagonists, particularly histamine receptor antagonists (antihistamines) inhibit Ebola and Marburg virus entry...
June 20, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28641998/construction-of-a-hepatitis-b-virus-neutralizing-chimeric-monoclonal-antibody-recognizing-escape-mutants-of-the-viral-surface-antigen-hbsag
#16
Forough Golsaz-Shirazi, Mohammad Mehdi Amiri, Samira Farid, Motahareh Bahadori, Felix Bohne, Sebastian Altstetter, Lisa Wolff, Tohid Kazemi, Jalal Khoshnoodi, Mohammad Hojjat-Farsangi, Michael Chudy, Mahmood Jeddi-Tehrani, Ulrike Protzer, Fazel Shokri
Hepatitis B virus (HBV) infection is a global burden on the health-care system and is considered as the tenth leading cause of death in the world. Over 248 million patients are currently suffering from chronic HBV infection worldwide and annual mortality rate of this infection is 686000. The "a" determinant is a hydrophilic region present in all antigenic subtypes of hepatitis B surface antigen (HBsAg), and antibodies against this region can neutralize the virus and are protective against all subtypes. We have recently generated a murine anti-HBs monoclonal antibody (4G4), which can neutralize HBV infection in HepaRG cells and recognize most of the escape mutant forms of HBsAg...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633988/a-cross-clade-h5n1-influenza-a-virus-neutralizing-monoclonal-antibody-binds-to-a-novel-epitope-within-the-vestigial-esterase-domain-of-hemagglutinin
#17
Subha Sankar Paul, Chee-Keng Mok, Tze-Minn Mak, Oi-Wing Ng, James Odame Aboagye, Teddy John Wohlbold, Florian Krammer, Yee-Joo Tan
The sporadic outbreaks of highly pathogenic H5N1 avian influenza virus have raised public health concerns. Monoclonal antibodies (MAbs) against hemagglutinin (HA) have been increasingly used successfully for therapeutic purposes. Previously, MAb 9F4, generated against clade 1 H5N1 HA, was observed to have cross-clade neutralizing efficacy and inhibited viral entry by preventing the pH-mediated conformational change of HA. Furthermore, mouse-human chimeric MAb 9F4 was found to retain high degrees of neutralizing activity...
June 19, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28633989/efficacy-and-cytotoxicity-in-cell-culture-of-novel-%C3%AE-hydroxytropolone-inhibitors-of-hepatitis-b-virus-ribonuclease-h
#18
Elena Lomonosova, Jil Daw, Aswin K Garimallaprabhakaran, Nana B Agyemang, Yashkumar Ashani, Ryan P Murelli, John E Tavis
Chronic Hepatitis B virus (HBV) infection is a major worldwide public health problem. Current direct-acting anti-HBV drugs target the HBV DNA polymerase activity, but the equally essential viral ribonuclease H (RNaseH) activity is unexploited as a drug target. Previously, we reported that α-hydroxytropolone compounds can inhibit the HBV RNaseH and block viral replication. Subsequently, we found that our biochemical RNaseH assay underreports efficacy of the α-hydroxytropolones against HBV replication. Therefore, we conducted a structure-activity analysis of 59 troponoids against HBV replication in cell culture...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28629988/4-azidocytidine-r1479-inhibits-henipaviruses-and-other-paramyxoviruses-with-high-potency
#19
Anne L Hotard, Biao He, Stuart T Nichol, Christina F Spiropoulou, Michael K Lo
The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4'-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae...
June 17, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28629987/anti-herpes-simplex-virus-type-1-activity-of-houttuynoid-a-%C3%A2-a%C3%A2-flavonoid-from-houttuynia-cordata-thunb
#20
Ting Li, Libao Liu, Hongling Wu, Shaodan Chen, Qinchang Zhu, Hao Gao, Xiongtao Yu, Yi Wang, Wenhan Su, Xinsheng Yao, Tao Peng
Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms...
June 17, 2017: Antiviral Research
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