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https://www.readbyqxmd.com/read/28430149/synthesis-and-antiviral-activity-of-novel-1-4-pentadien-3-one-derivatives-containing-a-1-3-4-thiadiazole-moiety
#1
Lu Yu, Xiuhai Gan, Dagui Zhou, Fangcheng He, Song Zeng, Deyu Hu
1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, ¹H-NMR, and (13)C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV...
April 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28418771/persistence-in-temporary-lung-niches-a-survival-strategy-of-lung-resident-memory-cd8-t-cells
#2
Shiki Takamura
Respiratory virus infections, such as those mediated by influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus (SARS-CoV), rhinovirus, and adenovirus, are responsible for substantial morbidity and mortality, especially in children and older adults. Furthermore, the potential emergence of highly pathogenic strains of influenza virus poses a significant public health threat. Thus, the development of vaccines capable of eliciting long-lasting protective immunity to those pathogens is a major public health priority...
April 18, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28416550/identification-and-optimization-of-thienopyridine-carboxamides-as-inhibitors-of-hiv-regulatory-complexes
#3
Robert L Nakamura, Mark A Burlingame, Shumin Yang, David C Crosby, Dale J Talbot, Kitty Chui, Alan D Frankel, Adam R Renslo
Viral regulatory complexes perform critical functions during virus replication and are important targets for therapeutic intervention. In HIV, the Tat and Rev proteins form complexes with multiple viral and cellular factors to direct transcription and export of the viral RNA. These complexes are composed of many proteins and are dynamic, making them difficult to fully recapitulate in vitro Therefore we developed a cell-based reporter assay to monitor the assembly of viral complexes for inhibitor screening. We screened a small molecule library and identified multiple hits that inhibit the activity of the viral complexes...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28405626/basic-scholarship-in-biosafety-is-critically-needed-to-reduce-risk-of-laboratory-accidents
#4
Ryan Ritterson, Rocco Casagrande
Our firm conducted a risk/benefit assessment of "gain-of-function" research, as part of the deliberative process following a U.S. moratorium on the research (U.S. Department of Health and Human Services, U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses, 2014). Due to significant missing but theoretically acquirable data, our biosafety assessment faced limitations, and we were forced to provide a relative, instead of absolute, measure of risk (Gryphon Scientific, LLC, Risk and Benefit Analysis of Gain of Function Research, 2016)...
March 2017: MSphere
https://www.readbyqxmd.com/read/28404843/overactive-egfr-signaling-leads-to-increased-fibrosis-after-sars-cov-infection
#5
Thiagarajan Venkataraman, Christopher Coleman, Matthew Frieman
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF) with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the Epidermal Growth Factor Receptor (EGFR) is critical to recovery from SARS-CoV induced tissue damage...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28393837/cryo-em-structures-of-mers-cov-and-sars-cov-spike-glycoproteins-reveal-the-dynamic-receptor-binding-domains
#6
Yuan Yuan, Duanfang Cao, Yanfang Zhang, Jun Ma, Jianxun Qi, Qihui Wang, Guangwen Lu, Ying Wu, Jinghua Yan, Yi Shi, Xinzheng Zhang, George F Gao
The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD)...
April 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28390872/the-role-of-epidermal-growth-factor-receptor-egfr-signaling-in-sars-coronavirus-induced-pulmonary-fibrosis
#7
REVIEW
Thiagarajan Venkataraman, Matthew B Frieman
Many survivors of the 2003 outbreak of severe acute respiratory syndrome (SARS) developed residual pulmonary fibrosis with increased severity seen in older patients. Autopsies of patients that died from SARS also showed fibrosis to varying extents. Pulmonary fibrosis can be occasionally seen as a consequence to several respiratory viral infections but is much more common after a SARS coronavirus (SARS-CoV) infection. Given the threat of future outbreaks of severe coronavirus disease, including Middle East respiratory syndrome (MERS), it is important to understand the mechanisms responsible for pulmonary fibrosis, so as to support the development of therapeutic countermeasures and mitigate sequelae of infection...
April 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28384506/extensive-diversity-of-coronaviruses-in-bats-from-china
#8
Xian-Dan Lin, Wen Wang, Zong-Yu Hao, Zhao-Xiao Wang, Wen-Ping Guo, Xiao-Qing Guan, Miao-Ruo Wang, Hong-Wei Wang, Run-Hong Zhou, Ming-Hui Li, Guang-Peng Tang, Jun Wu, Edward C Holmes, Yong-Zhen Zhang
To help reveal the diversity and evolution of bat coronaviruses we collected 1067 bats from 21 species in China. A total of 73 coronaviruses (32 alphacoronaviruses and 41 betacoronaviruses) were identified in these bats, with an overall prevalence of 6.84%. All newly-identified betacoronaviruses were SARS-related Rhinolophus bat coronaviruses (SARSr-Rh-BatCoV). Importantly, with the exception of the S gene, the genome sequences of the SARSr-Rh-BatCoVs sampled in Guizhou province were closely related to SARS-related human coronavirus...
April 3, 2017: Virology
https://www.readbyqxmd.com/read/28381569/group-a-rotaviruses-in-chinese-bats-genetic-composition-serology-and-evidence-for-bat-to-human-transmission-and-reassortment
#9
Biao He, Xiaohong Huang, Fuqiang Zhang, Weilong Tan, Jelle Matthijnssens, Shaomin Qin, Lin Xu, Zihan Zhao, Ling'en Yang, Quanxi Wang, Tingsong Hu, Xiaolei Bao, Jianmin Wu, Changchun Tu
Bats are natural reservoirs for many pathogenic viruses and increasing evidence supports that bats can also harbor group A rotaviruses (RVA), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains have been identified from African and Chinese bats, possessing completely novel genotype constellations or genotypes possibly originating from other mammals. However, all these data were mainly based on detection of RVA RNA, only present during acute infections, which does not permit assessment of the true exposure of a bat population to RVA...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28373583/sex-based-differences-in-susceptibility-to-severe-acute-respiratory-syndrome-coronavirus-infection
#10
Rudragouda Channappanavar, Craig Fett, Matthias Mack, Patrick P Ten Eyck, David K Meyerholz, Stanley Perlman
Pathogenic human coronaviruses (CoVs), such as the severe acute respiratory syndrome (SARS)-CoV and the Middle East respiratory syndrome-CoV, cause acute respiratory illness. Epidemiological data from the 2002-2003 SARS epidemic and recent Middle East respiratory syndrome outbreak indicate that there may be sex-dependent differences in disease outcomes. To investigate these differences, we infected male and female mice of different age groups with SARS-CoV and analyzed their susceptibility to the infection...
April 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28367882/severe-acute-respiratory-infection-sari-surveillance-for-hospitalized-patients-in-northern-vietnam-2011-2014
#11
Hang Khanh Le Nguyen, Son Vu Nguyen, Anh Phuong Nguyen, Phuong Mai Vu Hoang, Thanh Thi Le, Thach Co Nguyen, Huong Thu Hoang, Cuong Duc Vuong, Loan Thi Thanh Tran, Le Quynh Mai
Worldwide Severe Acute Respiratory Infections (SARI) are leading causes of hospitalization, morbidity and mortality in children. The aim of this study was to identify viral pathogens responsible for SARI in northern Vietnam from 2011 to 2014. METHODS: Throat swabs and tracheal aspirates were collected from SARI patients according to WHO Guidelines. Thirteen different viral pathogens (Influenza A(H1N)pdm09; A/H3N2; A/H5; A/H7 and B; Para influenza 1,2,3; RSV; HMPV; Adeno; SARS-CoV and Rhino) were tested by conventional/ real-time RT-PCR...
March 28, 2017: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28352124/discovery-and-genetic-analysis-of-novel-coronaviruses-in-least-horseshoe-bats-in-southwestern-china
#12
Lihua Wang, Shihong Fu, Yuxi Cao, Hailin Zhang, Yun Feng, Weihong Yang, Kai Nie, Xuejun Ma, Guodong Liang
To investigate bat coronaviruses (CoVs), we collected 132 rectal swabs and urine samples from five bat species in three countries in southwestern China. Seven CoVs belonging to distinct groups of severe acute respiratory syndrome (SARS)-like CoVs and α-CoVs were detected in samples from least horseshoe bats. Samples from other bat species were negative for these viruses, indicating that the least horseshoe bat represents one of the natural reservoirs and mixers for strains of CoVs and has a pivotal role in the evolution and dissemination of these viruses...
March 29, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-third-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#13
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
April 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28337328/structure-activity-relationship-study-of-ql47-a-broad-spectrum-antiviral-agent
#14
Yanke Liang, Melissanne de Wispelaere, Margot Carocci, Qingsong Liu, Jinhua Wang, Priscilla L Yang, Nathanael S Gray
Here we report the structure-activity relationship (SAR) investigations of QL-XII-47 (QL47), a compound that possesses broad-spectrum antiviral activity against dengue virus and other RNA viruses. A medicinal chemistry campaign initiated from QL47, a previously reported covalent BTK inhibitor, to derive YKL-04-085, which is devoid of any kinase activity when screened against a panel of 468 kinases and with improved pharmacokinetic properties. Both QL47 and YKL-04-085 are potent inhibitors of viral translation and exhibit cellular antiviral activity at 35-fold lower concentrations relative to inhibition of host-cell proliferation...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28333986/building-the-road-to-a-regional-zoonoses-strategy-a-survey-of-zoonoses-programmes-in-the-americas
#15
Melody J Maxwell, Mary H Freire de Carvalho, Armando E Hoet, Marco A N Vigilato, Julio C Pompei, Ottorino Cosivi, Victor J Del Rio Vilas
BACKGROUND: In recent years, global public health security has been threatened by zoonotic disease emergence as exemplified by outbreaks of H5N1 and H1N1 influenza, SARS, and most recently Ebola and Zika. Additionally, endemic zoonoses, such as rabies, burden countries year after year, placing demands on limited finances and personnel. To survey the baseline status of the emerging and endemic zoonoses programmes of the Latin American and the Caribbean (LAC) countries, the Pan American Health Organization (PAHO) conducted a survey of priority emerging and endemic zoonoses, countries´ prioritization criteria and methodologies, and suggestions to strengthen countries capacities and regional approaches to zoonoses control...
2017: PloS One
https://www.readbyqxmd.com/read/28266845/synthesis-antiviral-potency-in-vitro-admet-and-x-ray-structure-of-potent-cd4-mimics-as-entry-inhibitors-that-target-the-phe43-cavity-of-hiv-1-gp120
#16
Francesca Curreli, Young Do Kwon, Dmitry S Belov, Ranjith R Ramesh, Alexander V Kurkin, Andrea Altieri, Peter D Kwong, Asim K Debnath
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28257598/structural-basis-for-dimerization-and-rna-binding-of-avian-infectious-bronchitis-virus-nsp9
#17
Tingting Hu, Cheng Chen, Huiyan Li, Yanshu Dou, Ming Zhou, Deren Lu, Qi Zong, Yulei Li, Cheng Yang, Zhihui Zhong, Namit Singh, Honggang Hu, Rundong Zhang, Haitao Yang, Dan Su
The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA...
March 3, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28242560/viral-rewiring-of-cellular-lipid-metabolism-to-create-membranous-replication-compartments
#18
REVIEW
Jeroen Rpm Strating, Frank Jm van Kuppeveld
Positive-strand RNA (+RNA) viruses (e.g. poliovirus, hepatitis C virus, dengue virus, SARS-coronavirus) remodel cellular membranes to form so-called viral replication compartments (VRCs), which are the sites where viral RNA genome replication takes place. To induce VRC formation, these viruses extensively rewire lipid metabolism. Disparate viruses have many commonalities as well as disparities in their interactions with the host lipidome and accumulate specific sets of lipids (sterols, glycerophospholipids, sphingolipids) at their VRCs...
February 24, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28241456/evaluation-of-rice-resistance-to-southern-rice-black-streaked-dwarf-virus-and-rice-ragged-stunt-virus-through-combined-field-tests-quantitative-real-time-pcr-and-proteome-analysis
#19
Zhenchao Wang, Lu Yu, Linhong Jin, Wenli Wang, Qi Zhao, Longlu Ran, Xiangyang Li, Zhuo Chen, Rong Guo, Yongtian Wei, Zhongcheng Yang, Enlong Liu, Deyu Hu, Baoan Song
Diseases caused by southern rice black-streaked dwarf virus (SRBSDV) and rice ragged stunt virus (RRSV) considerably decrease grain yield. Therefore, determining rice cultivars with high resistance to SRBSDV and RRSV is necessary. In this study, rice cultivars with high resistance to SRBSDV and RRSV were evaluated through field trials in Shidian and Mangshi county, Yunnan province, China. SYBR Green I-based quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to quantitatively detect virus gene expression levels in different rice varieties...
February 22, 2017: Viruses
https://www.readbyqxmd.com/read/28220326/simultaneous-detection-of-severe-acute-respiratory-syndrome-middle-east-respiratory-syndrome-and-related-bat-coronaviruses-by-real-time-reverse-transcription-pcr
#20
Ji Yeong Noh, Sun-Woo Yoon, Doo-Jin Kim, Moo-Seung Lee, Ji-Hyung Kim, Woonsung Na, Daesub Song, Dae Gwin Jeong, Hye Kwon Kim
Since severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) share similar characteristics with respect to clinical signs, etiology, and transmission, methods for a rapid and accurate differential diagnosis are important. Therefore, the aim of this study was to develop a duplex real-time reverse transcription (RT)-PCR method for the simultaneous detection of these viruses. Primers and probes that target the conserved spike S2 region of human SARS-CoV, MERS-CoV, and their related bat CoVs were designed...
February 20, 2017: Archives of Virology
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