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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

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快速检测小麦种质资源遗传组成变化的非破坏性方法

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农业新技术新方法译丛 1993年第3期 7-9页

作者： ka.l.,jt 张艳敏

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外科口罩覆盖N95自吸过滤式防护口罩:增加泄漏风险

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中国感染控制杂志 2021年第3期20卷 277-278页

作者：谭彩霞(译) 吴安华(审校) Mueller jt karimi S Poterack ka 中南大学湘雅医院医院感染控制中心湖南长沙410008 不详

本报告通过对相关流体力学和密封压力的分析建模,论证了当N95自吸过滤式防护口罩(N95 FFR)被外科口罩、布口罩或医用口罩(统称为外科口罩)覆盖时,将增加颜面部与口罩之间密封泄漏的潜在风险。以前发表的关于呼吸器压力和泄漏的试验研究... 详细信息

本报告通过对相关流体力学和密封压力的分析建模,论证了当N95自吸过滤式防护口罩(N95 FFR)被外科口罩、布口罩或医用口罩(统称为外科口罩)覆盖时,将增加颜面部与口罩之间密封泄漏的潜在风险。以前发表的关于呼吸器压力和泄漏的试验研究也适用于此问题。在可预见的未来,正确使用N95 FFR仍将是保证医护人员安全的重要组成部分,特别是对于那些从事产生气溶胶操作(AGP)(如气管插管)的人员。在考虑泄漏风险时,重要的是要了解哪些因素可能会影响颜面部与口罩之间的密封性。N95 FFR的适配度和密封性会随着反复的穿戴和落纱而退化。据报道,一些N95 FFR再处理或回收技术可以加速这种退化。简而言之,N95型口罩密封性容易受损,可能会受到多种因素的影响。

关键词：口罩外科口罩自吸过滤式防护口罩医用口罩防护效果

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The development of roadside green swales in the Chinese Sponge City Program:Challenges and opportunities

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Frontiers of Engineering Management 2023年第4期10卷 566-581页

作者： lingwen lu Faith ka Shun Chan Matthew Johnson Fangfang Zhu Yaoyang Xu Key laboratory of Urban Environment and Health Ningbo Observation and Research StationInstitute of Urban EnvironmentChinese Academy of Sciences(CAS)Xiamen361021China School of Geographical Sciences Faculty of Science and EngineeringUniversity of Nottingham Ningbo ChinaNingbo315100China CAS Haixi Industrial Technology Innovation Center in Beilun Zhejiang Key Laboratory of Urban Environmental Processes and Pollution ControlNingbo315830China Water@leeds Research Institute University of LeedsLeeds LS29JTUK School of Geography University of NottinghamNottinghamshireNG72RDUK Department of Civil Engineering Faculty of Science and EngineeringUniversity of Nottingham Ningbo ChinaNingbo 315100China Zhejiang Key laboratory of Urban Environmental Processes and Pollution Control CAS Haixi Industrial Technology Innovation Center in BeilunNingbo 315830China

Roadside green swales have emerged as popular stormwater management infrastructure in urban areas,serving to mitigate stormwater pollution and reduce urban surface water ***,there is a limited understanding of the various types,structures,and functions of swales,as well as the potential challenges they may face in the *** recent years,China has witnessed a surge in the adoption of roadside green swales,especially as part of the prestigious Sponge City Program(SCP).These green swales play a crucial role in controlling stormwater pollution and conserving urban water resources by effectively removing runoff pollutants,including suspended solids,nitrogen,and *** review critically examines recent research findings,identifies key knowledge gaps,and presents future recommendations for designing green swales for effective stormwater management,with a particular emphasis on ongoing major Chinese infrastructure *** the growing global interest in bioswales and their significance in urban development,China's current classification of such features lacks a clear definition or specific consideration of ***,policymakers have often underestimated the adverse environmental effects of road networks,as reflected in existing laws and planning *** review argues that the construction and maintenance of roadside green swales should be primarily based on three critical factors:Wellthought-out road planning,suitable construction conditions,and sustainable long-term *** integration of quantitative environmental standards into road planning is essential to effectively address the challenge of pollution from rainfall *** combat pollution associated with roads,a comprehensive assessment of potential pollution loadings should be carried out,guiding the appropriate design and construction of green swales,with a particular focus on addressing the phenomenon of first *** of the major challenges faced in su

关键词： grass swale infiltration swale bioswale wet swale spongecity

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Urban agriculture as nature-based solutions:Three key strategies to tackle emerging issues on food security in Chinese cities under climatic and non-climatic challenges

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Frontiers of Engineering Management 2023年第4期10卷 736-741页

作者： Zhe ZHU Jiayu WANG Faith ka Shun CHAN Yuyao XU Gang lI Mengxia XU Wei-Qiang CHEN Yong-Guan ZHU Key laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China Department of Chemical and Environmental Engineering University of Nottingham Ningbo ChinaNingbo 315100China School of Geographical Sciences University of Nottingham Ningbo ChinaNingbo 315100China Water@leeds School of GeographyUniversity of LeedsLeedsLS29JTUK Research Base for Shenzhen Municipal Policy&Development Southern University of Science and TechnologyShenzhen 518000China New Materials Institute University of Nottingham Ningbo ChinaNingbo 315100China

1Introduction Achieving food and water security,according to the United Nations Sustainable Development Goals(SDGs),only requires a minimal environmental cost(Batalini de Macedo et al.,2022).However,in terms of agriculture,blindly devoting efforts to offset low-productivity farming or production techniques and industries,without systematic water,fertiliser,farm residue,tillage,and fallow management,will eventually interrupt the carbon sink under the soil and escalate greenhouse gas emissions,which is not helpful to meeting global climate ***,sciencebased land management practices are essential to decouple agricultural productivity from greenhouse gas emissions(Buscardo et al.,2021).

关键词： Sustainable climatic eventually

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A Conceptual Design Study for the Error Field Correction Coil Power Supply in jt-60SA

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Plasma Science and Technology 2013年第3期15卷 257-260页

作者： M.MATSUkaWA K.SHIMADA K.YAMAUCHI E.GAIO A.FERRO l.NOVEllO Japan Atomic Energy Agency 801-1 MukoyamaNakaIbaraki 311-0193Japan Consorzio RFX-EURATOM ENEA Association C.so Stati Uniti 435127 PadovaItaly Fusion for Energy Boltzmannstr 2 Garching 85748Germany

This paper describes a conceptual design study for the circuit configuration of the Error Field Correction Coil （EFCC） power supply （PS） to maximize the expected performance with reasonable cost in jt-60SA. The EFCC consists of eighteen sector coils installed inside the vacuum vessel, six in the toroidal direction and three in the poloidal direction, each one rated for 30 ka-turn. As a result, star point connection is proposed for each group of six EFCC coils installed cyclically in the toroidal direction for decoupling with poloidal field coils. In addition~ a six phase inverter which is capable of controlling each phase current was chosen as PS topology to ensure higher flexibility of operation with reasonable cost.

关键词： jt-60SA error field correction coil power supply inverter multi-phase

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中频交变磁场照射后小鼠的行为学变化

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中国组织工程研究与临床康复 2007年第48期11卷 9710-9713页

作者：赵洋夏启胜高艳华王淑秋赵天德刘新民唐劲天佳木斯大学基础医学院清华大学工程物理系北京市100084 清华大学工程物理系

目的:目前电磁辐射对生物体行为学方面的研究还很薄弱,设立不同磁场的强度和不同照射的周期,观察中频领域磁场照射对小鼠的自主活动和学习记忆的影响。方法:实验于2007-05-10/06-15在清华大学医学院和中国医学科学院药用植物研究所完成... 详细信息

目的:目前电磁辐射对生物体行为学方面的研究还很薄弱,设立不同磁场的强度和不同照射的周期,观察中频领域磁场照射对小鼠的自主活动和学习记忆的影响。方法:实验于2007-05-10/06-15在清华大学医学院和中国医学科学院药用植物研究所完成。①实验材料:磁场发生装置:中频交变磁场发生装置由清华大学工程物理系医学物理与工程研究所自主研发,可产生频率为40kHz,场强为28.8A/m,28.8ka/m的中频交变磁场。自主活动测试箱:中国医学科学院药用植物研究所提供,为一可封闭的金属箱,内置摄像头。4只黑色塑料测试桶分别置于箱子四角。水迷宫测试箱:中国医学科学院药用植物研究所提供。②实验动物及方法:将80只小鼠随机分为不同场强照射组和对照组。强磁场照射1组:11.6ka/m/40kHz,1h/d,连续照射7d。强磁场照射2组:11.6ka/m/40kHz,2h/d,连续照射7d。强磁场照射3组:11.6ka/m/40kHz,2h/d连续照射15d。弱磁场照射组:28.8ka/m/40kHz,2h/d,连续照射7d。对照组除了未放入磁场照射,其他条件与照射组一致。实验过程中对动物处置符合动物伦理学要求。③实验评估:观察其一般活动的改变,并采用自主活动测试箱和水迷宫测试箱进行测试,观察各组小鼠的自主活动和学习记忆的改变。结果:①一般行为观察:与对照组小鼠对比,经过中频交变磁场照射过的各组小鼠活跃度减低,毛色较差。强磁场照射3组(145G,2h/d,连续15d)于第11天和13天分别死亡1只。②自主活动检测结果:强磁场照射2,3组小鼠的运动路程、运动速度、运动时间明显低于对照组(P0.05)。结论:中频交变磁场照射会给小鼠的自发活动造成一定影响,对学习记忆没有影响。

关键词：中频交变磁场小鼠行为学

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颈动脉内膜中层厚度测量未改善高血压患者心血管风险预测

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中华高血压杂志 2014年第6期22卷 599-599页

作者： Bots Ml Groenewegen ka erson TJ Britton AR Dekker JM Engstrm G Evans GW de Graaf J Grobbee DE Hedblad B Hofman A Holewijn S Ikeda A kavousi M Kitagawa K Kitamura A Ikram MA lonn EM lorenz MW Mathiesen EB Nijpels G Okazaki S O'leary DH Polak JF Price JF Robertson C Rembold CM Rosvall M Rundek T Salonen jt Sitzer M Stehouwer CD Franco OH Peters SA den Ruijter HM 赵狄

颈动脉内膜中层厚度（carotid intima-media thickness,CIMT）是心血管风险的标志。目前仍不清楚颈总动脉CIMT测量能否改善高血压患者10年内首发心肌梗死或脑卒中的风险预测。研究人员获取正在进行的大规模荟萃分析：USE-IMT研究中的高... 详细信息

颈动脉内膜中层厚度（carotid intima-media thickness,CIMT）是心血管风险的标志。目前仍不清楚颈总动脉CIMT测量能否改善高血压患者10年内首发心肌梗死或脑卒中的风险预测。研究人员获取正在进行的大规模荟萃分析：USE-IMT研究中的高血压参与者（收缩压≥140和舒张压≥90 mm Hg,1mm Hg=0.133kPa）数据进行分析。

关键词：颈动脉内膜中层厚度高血压患者心血管风险风险预测厚度测量心肌梗死颈总动脉荟萃分析

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