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Self-assembled sialyllactosyl probes with aggregation-enhanced properties for ratiometric detection and blocking of influenza viruses

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Science Bulletin 2019年第24期64卷 1902-1909页

作者： Wei-Tao Dou Zhao-Yang Qin Jun Li Dong-Ming Zhou Xiao-Peng He Key Laboratory for Advanced Materials Feringa Nobel Prize Scientist Joint Research CenterSchool of Chernistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China Vaccine Research Center Key Laboratory of Molecular Virology&ImmunologyInstitut Pasteur of ShanghaiChinese Acadermy of SciencesShanghai 200031China

Infection and dissemination of influenza viruses(IVs) causes serious health concerns ***, effective tools for the accurate detection and blocking of IVs remain elusive. Here, we develop a new sialyllactosyl probe with self-assembled core-shell structure for the ratiometric detection and blocking of IVs. N,N'-diaryl-dihydrodibenzo[a,c]phenazines were used to form the core structure by hydrophobic assembly in an aqueous solution with an aggregation-enhanced blue fluorescence ***, dicyanomethylene-4 H-pyran-based sialyllactosides were used for self-assembly with the core structure, producing the sialyllactosyl probe that emits a red fluorescence due to Forster resonance energy transfer. The probe developed has been proven to be available for(1) the fluorescence ratiometric detection of IVs through selective interaction with the sialyllactosyl-binding proteins on the virus surface,and(2) effectively blocking the invasion of human-infecting IVs towards host cells as accentuated by the sialyllactosides on the surface of the probes.

关键词： Vibration-induced emission influenza viruses Ratiometric Fluorescence Glycoprobe

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Preexisting but biased T cell reactivity of seasonal influenza virus to human-infective avian influenza viruses

Preexisting but biased T cell reactivity of seasonal influen...

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第十一届全国免疫学学术大会

作者： ZHAO MIN LIU JUN TAN SHUGUANG LIU KEFANG CHAI YAN LUO JIEJIAN JIANG TAIJIAO WU AIPING BI YUHAI QUAN CHUANSONG QI JIANXUN GAO FU University of Chinese Academy of Sciences Institute of Microbiology Chinese Academy of Sciences Chinese Center for Disease Control and Prevention Institute of Biophysics Chinese Academy of Sciences

Background: Several newly emergent influenza viruses showed up in recent years, leading to epidemics and occasional pandemics. Researches focusing on cellular immunity are urged to be done. We aimed to systematically analyze of the cross-T cell reactivity and protection of seasonal flu to different avian flus and explore the molecular mechanisms. Methods: Here, we used ELISPOT assay and flow cytometry to evaluate pre-existing T cell responses, and then purified and crystalized MHC-peptide complexes to explain the mechanisms of the T cell response changes. Also, we did bioinformatics analysis to figure out the regular pattern of epitope ***: We found that there existed cross reactive T cell responses with bias among human infective influenza viruses and seasonal influenza viruses, and it showed that the T cell reactivity has bias to different influenza viruses. Epitopebased polygenesis trees displayed that H5N1 showed higher affinity with 09 p H1N1 than others. Furthermore, protection experiment in mice against H5N1 was better than that of H7N9, which was consistent with the trend of cross-reactive T cell responses in human. The MHC-peptide structures of a pair of epitopes lying in M1 protein showed a mutant in peptide could lead a dramatic immunogenicity change. Conclusions:(1)Our study showed a preexisting but biased T cell reactivity of seasonal influenza virus to human-infective avian influenza viruses.(2)Lacking of antibodies and limited amount of cross-reactive cellular immunities against the novel influenza virus implies higher threat of these viruses to humans, which has the potential to reemerge.(3)The loss of T-cell recognition had a regular pattern depending on the T cell epitope matrix. Epitopes in seasonal viruses may elicit more cross reactive T cell responses and serve better in near affinity viruses, which can be used in the vaccine design.

关键词： T cell responses influenza viruses epitopes MHC structures

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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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Taurolidine improved protection against highly pathogenetic avian influenza H5N1 virus lethal-infection in mouse model by regulating the NF-κB signaling pathway

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Virologica Sinica 2023年第1期38卷 119-127页

作者： Chaoxiang Lv Yuanguo Li Tiecheng Wang Qiqi Zhang Jing Qi Mingwei Sima Entao Li Tian Qin Zhuangzhuang Shi Fangxu Li Xuefeng Wang Weiyang Sun Na Feng Songtao Yang Xianzhu Xia Ningyi Jin Yifa Zhou Yuwei Gao College of Life Sciences Northeast Normal UniversityChangchunJilin130021China Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences.Changchun130122China College of Animal Medicine Jilin UniversityChangchun130000China College of Basic Medicine Changchun University of Chinese MedicineChangchun130117China College of Animal Science and Technology Jilin Agricultural UniversityChangchun130033China College of Life Sciences Shandong Normal UniversityJinan250014China

Taurolidine(TRD),a derivative of taurine,has anti-bacterial and anti-tumor effects by chemically reacting with cell-walls,endotoxins and exotoxins to inhibit the adhesion of ***,its application in antiviral therapy is seldom ***,we reported that TRD significantly inhibited the replication of influenza virus H5N1 in MDCK cells with the half-maximal inhibitory concentration(EC_(50))of 34.45μg/***,the drug inhibited the amplification of the cytokine storm effect and improved the survival rate of mice lethal challenged with H5N1(protection rate was 86%).Moreover,TRD attenuated virus-induced lung damage and reduced virus titers in mice *** of TRD reduced the number of neutrophils and increased the number of lymphocytes in the blood of H5N1 virus-infected ***,the drug regulated the NF-κB signaling pathway by inhibiting the separation of NF-κB and IκBa,thereby reducing the expression of inflammatory *** conclusion,our findings suggested that TRD could act as a potential anti-influenza drug candidate in further clinical studies.

关键词： influenza viruses H5N1 Taurolidine(TRD) Cytokine storms Inflammatory response NF-κB signaling pathway

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Efficacy and mechanisms of Traditional Chinese Medicine prevention and treatment for respiratory viruses

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Infectious Diseases Research 2023年第3期4卷 16-27页

作者： Fan-Fan Yang Jun Ren Bin Xu Jian Xu School of Medical Technology and Information Engineering Zhejiang Chinese Medical UniversityHangzhou 310053China School of Humanities and Management Zhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016China

Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life *** used antiviral drugs have obvious side effects and a narrow scope of *** viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine *** Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and *** multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus *** review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.

关键词： respiratory virus Traditional Chinese Medicine influenza viruses respiratory syncytial virus human rhinovirus novel coronavirus

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