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Analysis of proteins that interact with nucleocapsid protein of SARS-CoV using 15-mer phage-displayed library

Chinese Science Bulletin 2007年第15期52卷 2072-2080页

作者： liu ZhengXue WANG ZhanHui liu yingle DONG Wei QI YiPeng State Key Laboratory of Virology College of Life Science Wuhan University Wuhan 430072 China Biology Department Chongqing Three Gorges University Chongqing 404000 China

Analysis of proteins that interact with N protein of SARS-CoV using 15-mer phage-displayed library will help to explore the virus pathogenesis and to develop new drugs and vaccines against SARS. In this study,we cloned,expressed and purified N protein of SARS-CoV. This 46-kD N protein was verified by SDS-PAGE and Western-blot. Then,the peptides binding-specific to N protein were identified using 15-mer phage-displayed library. Surprisingly,all of the 89 clones from monoclonal ELISA were positive (S/N>2.1) and the result was further confirmed experimentally once again. Six N protein-binding pep-tides,designated separately as SNA1,SNA2,SNA4,SNA5,SNA9 and SNG11,were selected for se-quencing. Sequence analysis suggested that SNA5 shared approximatively 100% sequence identity to SNA4,SNA2,SNA9 and SNA1. In addition,the binding specificity of the 15-mer peptides with the SARS-CoV N protein was further demonstrated by blocking ELISA using the synthetical 15-mer peptide according to the deduced amino acid sequence of SNA5. Also,the deduced amino sequence of SNA5 was compared with proteins in translated database using the tblastx program,and the results showed that the proteins with the highest homology were Ubiquinol-cytochrome c reductase iron-sulfur sub-units (UCRI or UQCR),otherwise known as the Rieske iron-sulfur proteins (RISP). Notablely,in the 2Fe-2S redox centre of UCRI,there were 6 residues GGW(Y)F(Y)CP compatible to the residues (po-sition 2→7,GGWFCP7) of the NH2-terminal of the 15-mer peptide,which indicated higher binding specificity between the N protein of SARS-CoV and the redox centre of UCRI to some extent. Here,the possible molecular mechanisms of SARS-CoV N protein in the pathogenesis of SARS are discussed.

关键词：非典型肺炎核蛋白壳抗菌素细胞凋亡发病机制

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A Study of Two Cases Co-Infected with SARS-CoV-2 and Human Immunodeficiency Virus

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Virologica Sinica 2020年第6期35卷 849-852页

作者： Rong Zhang Xiaohua Chen Yuqing Huang Qi Zhang Yan Cheng Nan Zhang Haibo Zhang Bo Yang Fang liu yingle liu Ke Lan Department of Clinical Laboratory General Hospital of Southern Theater CommandPLAGuangzhou 510000China Department of Clinical Laboratory General Hospital of Central Theater CommandPLAWuhan 430000China State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan 430000China Department of Clinical Laboratory The 980st Hospital of the PLA Joint Logistics Support Force/Bethune International Peace HospitalShijiazhuang 050000China Department of Clinical Laboratory Jinling HospitalMedical School of Nanjing UniversityNanjing 210000China Department of Information General Hospital of Southern Theater CommandPLAGuangzhou 510000China Department of Radiology General Hospital of Central Theater CommandPLAWuhan 430000China

Dear Editor,Since December 2019,A new type of coronavirus pneumonia(coronavirus disease 2019,COVID-19)has become endemic in Wuhan,*** far,COVID-19 has developed into a global *** body’s immune system plays an importa... 详细信息

关键词： Infect Cases China.

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Identification of Caspase-cleavage site in the apoptosis suppressor protein P49 from the Spodoptera littoralis nucleopolyhedrovirus

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Chinese Science Bulletin 2003年第8期48卷 804-807页

作者： PEI Zifei, liu yingle, liu Qingzhen & QI Yipeng Institute of Virology, Wuhan University, Wuhan 430072, China Correspondence should be addressed to Qi Yipeng (e-mail: qiyipeng@ ***) Institute of Virology Wuhan University Wuhan China

The p49 gene from baculovirus Spodoptera lit-toralis nucleopolyhedrovirus (SlNPV) was able to suppress apoptosis of Sf9 cells induced by virus infection. Ectopically expressed P49 protein had the capacity to inhibit the activity of Caspases, being the executioner of apoptosis. Digestion of P49 with human Caspase or Bm-Caspase both yielded 10 and 40 kD fragments. Checking the sequence of P49, we found that the motif 91-TVTDG-95 of P49 was the sequence recog-nized by Caspases. The mutant of P49, Asp94Ala, could not be cut by both caspases and lost its caspases inhibition. Meanwhile, Thr91Ala mutant permitted the cleavage and partially retained its activity of caspases inhibition. We also found that P49 was a substrate of upstream initiator caspase and downstream effector Caspases, indicating that P49 was a broad specificity Caspase inhibitor.

关键词：凋亡抑制蛋白质皮肤病杆状病毒自卫机制

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Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan,China

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The Innovation 2022年第1期3卷 1-8页

作者： Qianyun liu Qing Xiong Fanghua Mei Chengbao Ma Zhen Zhang Bing Hu Junqiang Xu Yongzhong Jiang Faxian Zhan Suhua Zhou Li Tao Xianying Chen Ming Guo Xin Wang Yaohui Fang Shu Shen yingle liu Fang liu Li Zhou Ke Xu Changwen Ke Fei Deng Kun Cai Huan Yan Yu Chen Ke Lan State Key Laboratory of Virology Institute for Vaccine Research and Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhan 430072China Hubei Provincial Center for Disease Control and Prevention Wuhan 430079China Wuhan Jiang’an District Center for Disease Control and Prevention Wuhan 430000China National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Guangdong Provincial Center for Disease Control and Prevention Guangzhou 511430China

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity,but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 ***,we tested the sera from 248 COVID-19 convalescents around 1 year post-infection in Wuhan,the earliest known ***-CoV-2 immunoglobulin G(IgG)was well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 ***,varying degrees of immune escape was observed on the other tested variants in a patient-specific manner,with individuals showing remarkably broad neutralization *** immune escape can be largely attributed to several critical spike *** results suggest that SARS-CoV-2 can elicit long-lasting immunity but this is escaped by the emerging variants.

关键词： immunity maintained maintain

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Activation of the Ras/Raf/MEK Pathway Facilitates HCV Replication via Attenuation of the IFN-JAK-STAT Pathway

Activation of the Ras/Raf/MEK Pathway Facilitates HCV Replic...

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2012年鄂粤微生物学学术年会——湖北省暨武汉微生物学会成立六十年庆祝大会

作者： Qi Zhang Rui Gong Jing Qu Yijin Zhou Weiyong liu Mingzhou Chen yingle liu Ying Zhu Jianguo Wu State Key Laboratory of Virology College of Life SciencesWuhan University

Hepatitis C virus(HCV) is a major cause of chronic liver diseases worldwide, often leading to the development of hepatocellular carcinoma(HCC).Constitutive activation of Ras/Raf/MEK pathway is responsible for approximately 30%of cancers. Here,we attempted to address the correlation between activation of this pathway and HCV *** showed that knock-down of Raf1 inhibits HCV replication, while activation of Ras/Raf/MEK pathway by V12,a constitutively active form of Ras, stimulates HCV *** further demonstrated that this effect is regulated through the attenuation of IFN-JAK-STAT *** of Ras/Raf/MEK pathway down-regulates the expression of IFN-stimulated gene(ISG),attenuates the phosphorylation of STAT1/2,and inhibits the expression of interferon(alpha,beta and omega) receptor 1 and 2(IFNAR1/2).We also found that the down-regulation of IFNAR1 is caused by the increase in its phosphorylation level stimulated by the activity of Ras/Raf/MEK ***,we observed that HCV infection activates Ras/Raf/MEK ***,we propose that during HCV infection, Ras/Raf/MEK pathway is activated,which in turn attenuates IFN-JAK-STAT pathway, resulting in stimulating HCV replication.

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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

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Hyperuricacidemia as an independent predictor of paroxysmal atrial fibrillation

Hyperuricacidemia as an independent predictor of paroxysmal ...

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中华医学会心电生理和起搏分会第十次全国学术年会

作者： Tong liu,yingle Wu,Gang Xu,Ruyu Yuan,Guangping Li Department of Cardiology,Second Hospital of Tianjin Medical University 300211

Objective Uric acid(UA) is a cardiovascular risk marker associated with oxidative stress and ***,atrial fibrillation(AF) has been associated with inflammation and oxidative stress. The objective of this observational study was to investigate the association between UA levels and paroxysmal AF. Methods Consecutive patients with paroxysmal AF who were hospitalized in the Second Hospital of Tianjin Medical University from September 2011 to May 2012,were screened in this study.,We excluded subjects with acute coronary syndrome,congestive heart failure,valvular heart disease, congenital heart disease,cardiomyopathy,acute inflammatory conditions,thyroid *** final study population consisted of 106 patients,65 patients with paroxysmal atrial fibrillation were finally enrolled,and 41 age,sex matched-subjects without AF were served as the control *** baseline clinical data and laboratory examinations results were detected,left atrium diameter(LAD),left ventricular end-diastolic dimension(LVEDD) and left ventricular ejection fraction(LVEF) were determined by 2D-echocardiography. Results In univariate analysis,serum UA,LAD,LVEF,urea nitrogen and estimated glomerular filtration(eGFR) level were significantly increased in patients with paroxysmal AF compared with *** multivariate logistic regression analysis,the serum uric acid level(OR:5.935,P<0.05) and LAD(OR:1.144,P<0.05) were independent risk factors for the occurrence of paroxysmal AF. Conclusion We demonstrated that hyperuricacidemia is an independent risk factor for the development of paroxysmal *** larger studies are needed to evaluate this potential association as well as the underlying mechanisms.

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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

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Asymmetric Synthesis ofβ-CF3-β-Amino Acid via Aza-Morita-Baylis-Hillman Reaction Betweenα,β-Unsaturated Esters and 2-Methyl-N-（2,2,2-Trifluoroethylidene）Propane-2-Sulfinamide

Asymmetric Synthesis ofβ-CF3-β-Amino Acid via Aza-Morita-B...

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中国化学会第十二届全国氟化学会议

作者： Wei Yu yingle liu Yangen Huang~* College of Chemistry Chemical Engineering and Biotechnology Donghua University 2999 North Renmin Road Shanghai 201620 China College of Chemistry Chemical Engineering and Biotechnology Donghua University 2999 North Renmin Road Shangghai 201620 China

＜正＞Synthetic studies on fluorinatedα- andβ-amino acids as biologically relevant buiding blocks for synthesis of peptides andβ-lactams have attracted considerable attention in the past decades. 2-Methyl-N-（2,2,2-trifluoroethylidene）propane- 2-sulfinamide（1）,firstly reported by Kuduk in 2006 ,which was rapidly becoming a noticeable intermediate for the asymmetric synthesis of fluorinated

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Bcl-2 is recruited on ER viva RTN3 then its anti-apoptotic activity is reduced

Bcl-2 is recruited on ER viva RTN3 then its anti-apoptotic a...

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湖北省生物工程学会2004年年会

作者： Rong Xiang yingle liu Yipeng Qi Wei Dong Lei Zhu Laboratory of Molecular Virology, College of Life Sciences, Wuhan University Hubei, Wuhan, 430072, P.R.China

Bcl-2 serves as critical inhibitors of apoptosis triggered by a broad range of stimuli, mainly acting on the mitochondria. We found a member of the reticulon (RTN) ***3,which did not belong to the Bcl-2 family and was predominantly localized on the endoplasmic reticulum (ER) ,can interact with Bcl-2 in vitro and in vivo. Our results of flow cytometry identified that RTN3 can increase the localization of Bcl-2 on the ER, and

关键词： RTN3 Bcl-2 apoptosis endoplasmic reticulum

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