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SARS VIRUS

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https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-a-3-rd-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#1
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 3(rd) 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 1(st) and 2(nd) 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...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28337328/structure-activity-relationship-study-of-ql47-a-broad-spectrum-antiviral-agent
#2
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
#3
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
#4
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...
March 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28257598/structural-basis-for-dimerization-and-rna-binding-of-avian-infectious-bronchitis-virus-nsp9
#5
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 (MERS) 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28216045/discovery-of-2-oxopiperazine-dengue-inhibitors-by-scaffold-morphing-of-a-phenotypic-high-throughput-screening-hit
#9
Cyrille S Kounde, Hui-Quan Yeo, Qing-Yin Wang, Kah Fei Wan, Hongping Dong, Ratna Karuna, Ina Dix, Trixie Wagner, Bin Zou, Oliver Simon, Ghislain M C Bonamy, Bryan K S Yeung, Fumiaki Yokokawa
A series of 2-oxopiperazine derivatives were designed from the pyrrolopiperazinone cell-based screening hit 4 as a dengue virus inhibitor. Systematic investigation of the structure-activity relationship (SAR) around the piperazinone ring led to the identification of compound (S)-29, which exhibited potent anti-dengue activity in the cell-based assay across all four dengue serotypes with EC50<0.1μM. Cross-resistant analysis confirmed that the virus NS4B protein remained the target of the new oxopiperazine analogs obtained via scaffold morphing from the HTS hit 4...
February 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#10
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28187135/pathogen-cross-transmission-via-building-sanitary-plumbing-systems-in-a-full-scale-pilot-test-rig
#11
Michael Gormley, Thomas J Aspray, David A Kelly, Cristina Rodriguez-Gil
The WHO Consensus Document on the epidemiology of the SARS epidemic in 2003, included a report on a concentrated outbreak in one Hong Kong housing block which was considered a 'super-spreading event'. The WHO report conjectured that the sanitary plumbing system was one transmission route for the virus. Empty U-traps allowed the aerosolised virus to enter households from the sewerage system. No biological evidence was presented. This research reports evidence that pathogens can be aerosolised and transported on airstreams within sanitary plumbing systems and enter buildings via empty U-traps...
2017: PloS One
https://www.readbyqxmd.com/read/28159412/new-tools-in-nucleoside-toolbox-of-tick-borne-encephalitis-virus-reproduction-inhibitors
#12
Alexey A Orlov, Mikhail S Drenichev, Vladimir E Oslovsky, Nikolay N Kurochkin, Pavel N Solyev, Liubov I Kozlovskaya, Vladimir A Palyulin, Galina G Karganova, Sergey N Mikhailov, Dmitry I Osolodkin
Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'...
January 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28158275/early-endonuclease-mediated-evasion-of-rna-sensing-ensures-efficient-coronavirus-replication
#13
Eveline Kindler, Cristina Gil-Cruz, Julia Spanier, Yize Li, Jochen Wilhelm, Huib H Rabouw, Roland Züst, Mihyun Hwang, Philip V'kovski, Hanspeter Stalder, Sabrina Marti, Matthias Habjan, Luisa Cervantes-Barragan, Ruth Elliot, Nadja Karl, Christina Gaughan, Frank J M van Kuppeveld, Robert H Silverman, Markus Keller, Burkhard Ludewig, Cornelia C Bergmann, John Ziebuhr, Susan R Weiss, Ulrich Kalinke, Volker Thiel
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28148787/sars-coronavirus-nucleocapsid-inhibits-type-i-interferon-production-by-interfering-with-trim25-mediated-rig-i-ubiquitination
#14
Yong Hu, Wei Li, Ting Gao, Yan Cui, Yanwen Jin, Ping Li, Qingjun Ma, Xuan Liu, Cheng Cao
Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a coronavirus (SARS-CoV) that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28148786/neurovirulent-murine-coronavirus-jhm-sd-uses-cellular-zinc-metalloproteases-for-virus-entry-and-cell-cell-fusion
#15
Judith M Phillips, Tom Gallagher, Susan R Weiss
The coronavirus S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry of the highly neurovirulent MHV strain JHM...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28134071/everyday-dangers-the-impact-infectious-disease-has-on-the-health-of-paramedics-a-scoping-review
#16
Brodie Thomas, Peter O'Meara, Evelien Spelten
BACKGROUND: Paramedics respond to emergency scenes in often uncontrolled settings without being aware of potential risks. This makes paramedicine one of the most dangerous occupations. One of these dangers is the risk of contracting infectious diseases. Research in this area is predominantly focused on compliance in the use of protective equipment, attitudes and perceptions of paramedics, infectious disease policy, and exposure rates to blood and body fluids. The purpose of this scoping review was to determine what is known about the impact of infectious disease on the health of paramedics...
January 30, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28131392/improving-the-selection-and-development-of-influenza-vaccine-viruses-report-of-a-who-informal-consultation-on-improving-influenza-vaccine-virus-selection-hong-kong-sar-china-18-20-november-2015
#17
Hampson Alan, Barr Ian, Cox Nancy, Donis Ruben O, Hirve Siddhivinayak, Jernigan Daniel, Katz Jacqueline, McCauley John, Motta Fernando, Odagiri Takato, John S Tam, Waddell Anthony, Webby Richard, Ziegler Thedi, Zhang Wenqing
Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies...
January 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28128492/beyond-attachment-roles-of-dc-sign-in-dengue-virus-infection
#18
Ping Liu, Marc Ridilla, Pratik Patel, Laurie Betts, Emily Gallichotte, Lidea Shahidi, Nancy L Thompson, Ken Jacobson
Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization...
January 27, 2017: Traffic
https://www.readbyqxmd.com/read/28121202/progress-of-middle-east-respiratory-syndrome-coronavirus-vaccines-a-patent-review
#19
Jiwon Choi, Mi-Gyeong Kim, Yu-Kyoung Oh, Young Bong Kim
Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a new pathogen, causing severe complications and a high case fatality rate. No direct treatments are available as yet, highlighting the importance of prevention through suitable vaccination regimes. The viral spike (S) protein has been characterized as a key target antigen for vaccines. In particular, S protein domains have been utilized to produce high titers of neutralizing antibodies. Areas covered: Since the first report of MERS-CoV infection, a limited number of MERS-CoV-specific patents have been filed...
January 25, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28077633/surveillance-of-bat-coronaviruses-in-kenya-identifies-relatives-of-human-coronaviruses-nl63-and-229e-and-their-recombination-history
#20
Ying Tao, Mang Shi, Christina Chommanard, Krista Queen, Jing Zhang, Wanda Markotter, Ivan V Kuzmin, Edward C Holmes, Suxiang Tong
Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya from 2007 to 2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the breakpoint located near 5' and 3' ends of the spike (S) protein gene...
March 1, 2017: Journal of Virology
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