检索结果-南通市图书馆

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper Fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-yun Wang yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-yung yuen Shuofeng yuan State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Pathogenesis of pandemic H1N1 2009 influenza virusinfection and the implication on management

引用

Frontiers of Medicine 2010年第2期4卷 147-156页

作者： Kelvin Kai-Wang TO Iris Wai-Sum LI Ivan Fan-Ngai HUNG Vincent Chi-Chung CHENG Kwok-yung yuEN carol yu Center for infection Department of MicrobiologyThe University of Hong KongHong Kong SARChina

The pandemic H1N12009 inﬂuenza virus has caused theﬁrst inﬂuenza pandemic of the 21st century,leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the *** in science and technology have allowed very detailed study on the pathogenesis of this novel virus,and many have already been published in less than a year after the start of the *** generated from cell lines,animal models,and clinical data analysis has provided us with greater understanding of the behavior of this virus and the associated host *** new knowledge will allow us to formulate scientiﬁcally sound and evidence-based management plans.

关键词： inﬂuenza A virus,H1N1 subtype pandemic pathogenesis virulence factors immunity management,antiviral

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Leptotrichia hongkongensis ***.,a novel Leptotrichia species with the oral cavity as its natural reservoir

引用

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第6期11卷 391-401页

作者： Patrick C. Y. WOO Samson S. Y. WONG Jade L. L. TENG Kit-Wah LEUNG Antonio H. Y. NGAN Dong-qing ZHAO Herman TSE Susanna K. P. LAU Kwok-yung yuEN State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong Hong Kong China Research centre of infection and Immunology The University of Hong Kong Hong Kong China Department of Microbiology The University of Hong Kong Hong Kong China carol yu centre for infection The University of Hong Kong Hong Kong China

A straight, non-sporulating, Gram-variable bacillus (HKU24T) was recovered from the blood culture of a patient with metastatic breast carcinoma. After repeated subculturing in BACTEC Plus Anaerobic/F blood culture broth, HKU24T grew on brucella agar as non-hemolytic, pinpoint colonies after 96 h of incubation at 37 °C in an anaerobic environment and aerobic environment with 5% CO2. Growth was enhanced with a streak of Staphylococcus aureus. HKU24T was non-motile and catalase-negative, but positive for alkaline phosphatase, β-glucosidase, and α-glucosidase. It hydrolyzed phenylphosphonate and reduced resazurin. 16S rRNA, groEL, gyrB, recA, and rpoB sequencing showed that HKU24T occupies a distinct phylogenetic position among the Leptotrichia species, being most closely related to Leptotrichia trevisanii. Using HKU24T groEL, gyrB, recA, and rpoB gene-specific primers, fragments of these genes were amplified from one of 20 oral specimens. Based on phenotypic and genotypic characteristics, we propose a new species, Leptotrichia hongkongensis sp. nov., to describe this bacterium.

关键词： Leptotrichia hongkongensis Bacterium Blood culture Anaerobic bacteria Novel species

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Romance of the three domains:how cladistics transformed the classifi cation of cellular organisms

引用

Protein & Cell 2013年第9期4卷 664-676页

作者： Chi-Chun Ho Susanna K.P.Lau Patrick C.Y.Woo Department of Microbiology The University of Hong KongHong KongChina State Key Laboratory of Emerging Infectious Diseases The University of Hong KongHong KongChina Research centre of infection and Immunology The University of Hong KongHong KongChina carol yu centre of infection The University of Hong KongHong KongChina

Cladistics is a biological philosophy that uses genealogi-cal relationship among species and an inferred sequence of divergence as the basis of classifi *** review critically surveys the chronological development of bio-logical classification from Aristotle through our post-genomic era with a central focus on *** 1957,Julian Huxley coined cladogenesis to denote splitting from *** 1960,the English translation of Willi Hennig’s 1950 work,Systematic Phylogenetics,was published,which received strong opposition from phenet-icists,such as numerical taxonomists Peter Sneath and Robert Sokal,and evolutionary taxonomist,Ernst Mayr,and sparked acrimonious debates in *** 1977-1990,Carl Woese pioneered in using small subunit rRNA gene sequences to delimitate the three domains of cellu-lar life and established major prokaryotic *** has since dominated *** being compatible with modern microbiological observations,*** with unusual phenotypes,restricted expression of charac-teristics and occasionally being uncultivable,increasing recognition of pervasiveness and abundance of horizon-tal gene transfer has challenged relevance and validity of *** mosaic nature of eukaryotic and prokary-otic genomes was also gradually *** the mid-2000s,high-throughput and whole-genome sequencing became routine and complex geneologies of organisms have led to the proposal of a reticulated web of *** genomics only indirectly leads to understanding of func-tional adaptations to ecological niches,computational modeling of entire organisms is underway and the gap between genomics and phenetics may soon be *** are not expected to settle as taxonomic classifi cations shall remain subjective to serve the human scientist,not the classifi ed.

关键词： cladistics phenetics phylogeny classifi ca-tion evolution

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Two-dimensional gel electrophoresis in bacterial proteomics

引用

Protein & Cell 2012年第5期3卷 346-363页

作者： Shirly O.T.Curreem Rory M.Watt Susanna K.P.Lau Patrick C.Y.Woo Department of Microbiology The University of Hong KongQueen Mary HospitalHong KongChina Oral Biosciences Faculty of DentistryThe University of Hong KongQueen Mary HospitalHong KongChina State Key Laboratory of Emerging Infectious Diseases Department of MicrobiologyThe University of Hong KongQueen Mary HospitalHong KongChina Research centre of infection and Immunology The University of Hong KongQueen Mary HospitalHong KongChina carol yu centre of infection The University of Hong KongHong KongChina

Two-dimensional gel electrophoresis(2-DE)is a gel-based technique widely used for analyzing the pro-tein composition of biological *** is capable of resolving complex mixtures containing more than a thousand protein components into individual protein spots through the coupling of two orthogonal bio-physical separation techniques:isoelectric focusing(first dimension)and polyacrylamide gel electrophore-sis(second dimension).2-DE is ideally suited for ana-lyzing the entire expressed protein complement of a bacterial cell:its *** relative simplicity and good reproducibility have led to 2-DE being widely used for exploring proteomics within a wide range of envi-ronmental and medically-relevant *** we give a broad overview of the basic principles and his-torical development of gel-based proteomics,and how this powerful approach can be applied for studying bacterial biology and *** highlight specific 2-DE applications that can be used to analyze when,where and how much proteins are *** links between proteomics,genomics and mass spectrometry are *** explore how proteomics involving tandem mass spectrometry can be used to analyze(post-translational)protein modifications or to identify proteins of unknown origin by de novo peptide *** use of proteome fractionation tech-niques and non-gel-based proteomic approaches are also *** highlight how the analysis of pro-teins secreted by bacterial cells(secretomes or exo-proteomes)can be used to study infection processes or the immune *** review is aimed at non-specialists who wish to gain a concise,compre-hensive and contemporary overview of the nature and applications of bacterial proteomics.

关键词： two-dimensional gel electrophoresis bacte-ria proteomics

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

引用

Acta Pharmaceutica Sinica B 2024年第5期14卷 2077-2096页

作者： Cheng Qian yueke Zhou Teng Zhang Guanglu Dong Mengyao Song yu Tang Zhonghong Wei Suyun yu Qiuhong Shen Wenxing Chen Jaesung P.Choi Juming Yan Chongjin Zhong Li Wan Jia Li Aiyun Wang Yin Lu Yang Zhao Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China School of Medicine&Holistic Integrative Medicine Nanjing University of Chinese MedicineNanjing 210023China centre for Inflammation Faculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China Department of General Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical School Faculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

关键词： Salvianic acid A Tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Generation and Application of a Luciferase Reporter Virus Based on Yellow Fever Virus 17D

引用

Virologica Sinica 2021年第6期36卷 1456-1464页

作者： Dan Li Jing-Long Ye Zhong-yu Liu The centre for infection and Immunity Studies School of MedicineSun Yat-Sen UniversityGuangzhou 510006China

Yellow fever virus(YFV) is a re-emerging virus that can cause life-threatening yellow fever disease in *** the availability of an effective vaccine,little is known about the replication mechanism of YFV,and there are still no available specific anti-YFV ***,by introducing the Renilla luciferase gene(Rluc) into an infectious clone of YFV vaccine strain 17 D,we generated a recombinant virus 17 D-Rluc.2 A via reverse genetics *** 17 D-Rluc.2 A had similar plaque morphology and comparable in vitro growth characteristics with its parental ***,the reporter luciferase was efficiently expressed in 17 D-Rluc.2 A-infected mammalian and mosquito cells,and there was a good linear correlation between intracellular luciferase expression and extracellular infectious virion ***,by a combination of the 17 D-Rluc.2 A reporter virus and selective 2’-hydroxyl acylation analyzed by primer extension(SHAPE)technology,the conserved 5’-SLA element was shown to be essential for YFV replication,highlighting the capability of17 D-R1 uc.2 A in the investigation of YFV *** last,we demonstrated that two compounds with distinct anti-viral mechanisms can effectively inhibit the viral propagation in 17 D-Rluc.2 A-infected cells,demonstrating its potential application in the evaluation of anti-viral *** together,the 17 D-Rluc.2 A serves as a useful tool for the study of YFV replication and anti-YFV medicine development.

关键词： Yellow fever virus(YFV) 17D Reporter virus Cis-acting RNA elements Anti-viral medicines

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

引用

Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying yu Pengfei yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty Institute for infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Lemierre’s Syndrome Associated With Campylobacter rectus Bacteremia

引用

Infectious Microbes & Diseases 2019年第1期1卷 27-29页

作者： Derek L.L.Hung Jade L.L.Teng Susanna K.P.Lau Patrick C.Y.Woo Department of Microbiology The University of Hong KongHong KongChina State Key Laboratory of Emerging Infectious Diseases The University of Hong KongHong KongChina carol yu centre for infection The University of Hong KongHong KongChina Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases The University of Hong KongHong KongChina

Introduction Campylobacter rectus is a Gram-negative,anaerobic rod,first described in 1981 as Wolinella recta,subsequently re-classified to Campylobacter based on phylogenetic analysis in 1991.1 It is found in the oral cavity and gastrointestinal tract,and is mainly implicated in oral and periodontal *** far,there are only a handful of case reports in the literature describing extra-oral invasive *** infections.2–6 Recently,we described a case of fatal *** infection,due to subdural empyema and ruptured mycotic intracranial aneurysm.2 In this article,we report a case of Lemierre’s syndrome associated with *** bacteremia.

关键词： Lemierre’s syndrome Campylobacter rectus bacteremia

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Peptidic defective interfering gene nanoparticles against Omicron,Delta SARS-CoV-2 variants and influenza A virus in vivo

引用

Signal Transduction and Targeted Therapy 2022年第9期7卷 3484-3493页

作者： Hanjun Zhao Chuyuan Zhang Hoiyan Lam Xinjie Meng Zheng Peng Man Lung Yeung Jasper Fuk-Woo Chan Kelvin Kai-Wang To Kwok-yung yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina Department of Infectious Disease and Microbiology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinceChina carol yu centre for infection The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina

Defective interfering genes(DIGs)are short viral genomes and interfere with wild-type viral ***,we demonstrate that the new designed SARS-CoV-2 DIG(CD3600)can significantly inhibit the replication of SARS-CoV-2 including Alpha,Delta,Kappa and Omicron variants in human HK-2 cells and influenza DIG(PAD4)can significantly inhibit influenza virus replication in human A549 *** dose of influenza DIGs prophylactically protects 90%mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral *** further investigate the gene delivery vector in the respiratory tract,a peptidic TAT2-P1&LAH4,which can package genes to form small spherical nanoparticles with high endosomal escape ability,is demonstrated to dramatically increase gene expression in the lung ***2-P1&LAH4,with the dual-functional TAT2-P1(gene-delivery and antiviral),can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster *** peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo,which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.

关键词： influenza vivo Delta

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：