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Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

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Protein & Cell 2020年第10期11卷 723-739页

作者： Rui Xiong Leike Zhang Shiliang Li Yuan Sun Minyi Ding Yong Wang Yongliang Zhao Yan Wu Weijuan shang Xiaming Jiang jiwei shan Zihao Shen Yi Tong Liuxin Xu Yu Chen Yingle Liu Gang Zou Dimitri Lavillete Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan 430072China shanghai Key Laboratory of New Drug Design State Key Laboratory of Bioreactor EngineeringSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China CAS Key Laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus ***,we identified two potent inhibitors of human DHODH,S312 and S416,with favorable drug-likeness and pharmacokinetic profiles,which all showed broad-spectrum antiviral effects against various RNA viruses,including influenza A virus,Zika virus,Ebola virus,and particularly against ***,S416 is reported to be the most potent inhibitor so far with an EC5o of 17 nmol/L and an SI value of 10,505.88 in infec-ted *** results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out *** work demonstrates that both S312/S416 and old drugs(Leflunomide/Teriflunomide)with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide,no matter such viruses are mutated or not.

关键词： de novo pyrimidine biosynthesis DHODH inhibitors SARS-CoV-2 influenza viruses virus replication immuno-regulation

Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

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Protein & Cell 2021年第1期12卷 76-80页

Figure *** of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and *** detailed descriptions of the discovery workflow are in *** analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 *** analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument.

关键词： Figure discovery ODH

高职体育保健课“课内外一体化”策略研究——以浙江东方职业技术学院为例

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商丘职业技术学院学报 2015年第5期14卷 132-134页

作者：单继伟浙江东方职业技术学院浙江温州325011

关注病、残、弱及部分身体异常学生的体育需求是创建和谐校园的重要方面.然而这部分学生往往会因为身体等原因造成锻炼自信心不足,甚至远离运动.为此,文章认为高职体育保健课应发挥课堂教学优势为学生教授锻炼方法,提高锻炼信心的同时,... 详细信息

关注病、残、弱及部分身体异常学生的体育需求是创建和谐校园的重要方面.然而这部分学生往往会因为身体等原因造成锻炼自信心不足,甚至远离运动.为此,文章认为高职体育保健课应发挥课堂教学优势为学生教授锻炼方法,提高锻炼信心的同时,还应创造条件为学生提供课外体育锻炼的机会,即"课内外一体化"教学模式.

关键词：高职体育保健课课内外一体化

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现代普通高校体育馆的规划与设计研究

湖北成人教育学院学报 2013年第4期19卷 60-62页

作者：单继伟浙江东方职业技术学院基础部浙江温州325011

体育馆是高校校园建设中的一个重要组成部分,随着高校体育资源的社会化发展,高校体育馆被赋予更多的功能。在规划和设计中应着重整体布局,优化选址,并根据学校的实际需求合理定位,突出馆内空间的弹性化组合。

关键词：高校综合性体育馆规划与设计

船舶运输散装盐时的Limewashing作业

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航海技术 2022年第4期 72-75页

作者：杜柏松单继伟浙江海洋大学船舶与海运学院大连国合海事技术服务有限公司

在船舶运输大宗散装盐的过程中,因为散装盐对金属具有较强的腐蚀性,运输途中可能会对船舶货舱钢材结构、钢材管路等产生腐蚀,破坏货舱的结构和强度,影响船舶安全。为了保护货舱,在船舶进行散装盐的运输业务中,船舶备舱尤其重要。Limewas... 详细信息

在船舶运输大宗散装盐的过程中,因为散装盐对金属具有较强的腐蚀性,运输途中可能会对船舶货舱钢材结构、钢材管路等产生腐蚀,破坏货舱的结构和强度,影响船舶安全。为了保护货舱,在船舶进行散装盐的运输业务中,船舶备舱尤其重要。Limewashing(喷涂石灰水后洗舱)作业是计划运输散装盐的船舶必须要做的一项重要备舱工作,因备舱质量要求高、操作过程中存在较大风险,作业不当不仅会严重影响船员身体健康,还会延误船期给船东和租家造成不必要的经济损失。

关键词：船舶运输运输业务运输途中船舶安全石灰水散装操作过程

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澳大利亚丹皮尔港盐码头移泊操纵

航海技术 2023年第1期 1-3页

作者：杜柏松单继伟浙江海洋大学大连国合海事技术服务有限公司

船舶在港进行移泊作业,常受泊位或码头作业设备等条件的限制,若操纵不当,会导致断缆、擦碰码头或碰撞他船等事故发生。澳大利亚丹皮尔港(Port of Dampier)盐码头由于其特殊的泊位结构和装载机械配备,船舶需多次移泊才能完成装货作业。... 详细信息

船舶在港进行移泊作业,常受泊位或码头作业设备等条件的限制,若操纵不当,会导致断缆、擦碰码头或碰撞他船等事故发生。澳大利亚丹皮尔港(Port of Dampier)盐码头由于其特殊的泊位结构和装载机械配备,船舶需多次移泊才能完成装货作业。该码头移泊距离长,仅允许采用缆绳(长倒缆等)操纵,曾发生多起船舶碰撞码头和断缆事故。为了避免类似事故发生,本文基于航海实践,从该港泊位情况、移泊操纵方法.

关键词：装载机械移泊船舶碰撞事故发生码头作业丹皮尔澳大利亚航海实践

体质和职业双需求下高职体育课程模块化研究——以服务类专业为例

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湖北体育科技 2014年第11期33卷 1016-1018页

作者：孙永梅单继伟浙江东方职业技术学院基础部浙江温州325011

以服务类专业学生为研究对象,在提高学生基本身体素质的基础上,有针对性地培养职业所需的特殊身体素质,提出了"两阶段"、"四模块"的模块化设计方案,以提高学生对服务类职业的适应能力。

关键词：高职体育模块化服务类专业

Discovery and Rational Design of Natural Product-derived Analogs as Novel and Long-acting DPP-4 Inhibitors

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Discovery and Rational Design of Natural Product-derived Ana...

Mechanism and morphology evolution of the O phase transformation in Ti-22Al-25Nb alloy

中国化学会第十一届全国天然有机化学学术会议

作者： Shiliang Li Hongling Xu Fangshu Wu Shichao Cui Youli Zhang Chun Qin Qian Jiao jiwei shan Ming Zhang Qiao Yin Xiaofeng Liu Rui Wang Lili Zhu Mingbo Su Jia Li Yufang Xu Hualiang Jiang Jingya Li Zhenjiang Zhao Honglin Li shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and Technology State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences

＜正＞Diabetes is a fast growing worldwide chronic metabolic ***-4 has been proved one of the most effective targets for T2DM treatment by the commercial success of ***,iso-daphnetin,a natural product,was identified t...

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Journal of Materials Science & Technology 2021年第30期89卷 97-106页

作者： Zong Yingying Wang jiwei Shao Bin Tang Wei shan Debin National Key Laboratory for Precision Hot Processing of Metals Harbin Institute of TechnologyHarbin150001China

The phase transformation and microstructure in Ti-22Al-25Nb alloy are extremely *** this work,the morphology evolution of the O phase during the heating and cooling process was investigated by electron backscatter diffraction(EBSD)and first-principles *** results show that the O→α_(2)phase transformation process during the heating process is as follows:spheroidization of the O phase occurs first,then theα_(2)phase nucleates in the spheroidized O phase,grows and replaces the O phase,completing the O→α_(2)phase *** the meanwhile,the diffusion of Nb from Nb-poor O to Nb-rich B2 phases is a back-diffusion *** to first-principles calculations,the driving force of the O→α_(2)phase transformation is the difference in the free energies of formation for the two phases(0.09 eV/atom).When the Nb content is greater than 15.625%,the lattice distortion of theα_(2)phase sharply increases,and the distortion energy drives the back-diffusion of *** the cooling process,theα_(2)→O phase transformation is difficult and slow due to the difficult diffusion of Nb from the B2 toα_(2)*** holding for 60 min at 960℃,the coarseα_(2)phase gradually transforms to the O phase from the margin to the inside,forming a dispersed mixed structure of the O andα_(2)*** the B2→O transformation,the nucleation of the O phase induces a high stress region,in the range of approximately 200 nm.

关键词： Ti-22Al-25Nb alloy Phase transformation Microstructure O phase First-principles