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Protein & Cell 2010年第4期1卷 342-354页

作者： Shibo Jiang Runming Li Lanying Du Shuwen Liu lindsley f.kimball research institute New York Blood CenterNew YorkNY 10065USA School of.Pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China

Seasonal inf.uenza epidemics and inf.uenza pandemics caused by inf.uenza A virus(IAV)has resulted in millions of.deaths in the world.The development of.anti-IAV vaccines and therapeutics is urgently needed f.r prevention and treatment of.IAV inf.ction and f.r controlling f.ture inf.uenza pandemics.Hemagglutinin(HA)of.IAV plays a critical role in viral binding,f.sion and entry,and contains the major neutralizing epitopes.Theref.re,HA is an attractive target f.r developing anti-IAV drugs and vaccines.Here we have reviewed the recent progress in study of.conf.rmational changes of.HA during viral f.sion process and development of.HA-based antiviral therapeutics and vaccines.

关键词： inf.uenza A virus hemagglutinin viral entry antiviral drugs vaccines

Development of.small-molecule viral inhibitors targeting various stages of.the lif. cycle of.emerging and re-emerging viruses

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f.ontiers of.Medicine 2017年第4期11卷 449-461页

作者： Xiaohuan Wang Peng Zou f.n Wu Lu Lu Shibo Jiang Shanghai Public Health Clinical Center & Key Laboratory of.Medical Molecular Hrology of.MOE/MOH of.School of.Basic Medical Sciences Fudan University Shanghai 200032 China lindsley f. kimball research institute New York Blood Center New York NY 10065 USA

In recent years, unexpected outbreaks of.inf.ctious diseases caused by emerging and re-emerging viruses have become more f.equent, which is possibly due to environmental changes. These outbreaks result in the loss of.lif. and economic hardship. Vaccines and therapeutics should be developed f.r the prevention and treatment of.inf.ctious diseases. In this review, we summarize and discuss the latest progress in the development of.small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interf.re with the specif.c steps of.viral lif. cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane f.sion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic ef.ect against various emerging and re-emerging viruses. We also discuss some general strategies f.r developing small-molecule viral inhibitors.

关键词： emerging and re-emerging viruses small-molecule inhibitor coronavirus Ebola virus Zika virus lif. cycle

Neutralizing antibodies f.r the prevention and treatment of.COVID-19

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Cellular & Molecular Immunology 2021年第10期18卷 2293-2306页

作者： Lanying Du Yang Yang Xiujuan Zhang lindsley f.kimball research institute New York Blood CenterNew YorkNYUSA Roy J.Carver Department of.Biochemistry Biophysics and Molecular BiologyIowa State UniversityAmesIAUSA

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)initiates the inf.ction process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain(RBD)in the S1 subunit of.the viral spike(S)protein.This event is f.llowed by virus–cell membrane f.sion mediated by the S2 subunit,which allows virus entry into the host cell.Theref.re,the SARS-CoV-2 S protein is a key therapeutic target,and prevention and treatment of.coronavirus disease 2019(COVID-19)have f.cused on the development of.neutralizing monoclonal antibodies(nAbs)that target this protein.In this review,we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date,with a f.cus on the N-terminal domain and RBD of.the S protein.We also describe the roles that binding af.inity,neutralizing activity,and protection provided by these nAbs play in the prevention and treatment of.COVID-19 and discuss the potential to improve nAb ef.iciency against multiple SARSCoV-2 variants.This review provides important inf.rmation f.r the development of.ef.ective nAbs with broad-spectrum activity against current and f.ture SARS-CoV-2 strains.

关键词： SARS-CoV-2 Spike protein Neutralization Monoclonal antibodies COVID-19

The development of.HIV vaccines targeting gp41 membrane-proximal external region （MPER）： challenges and prospects

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Protein & Cell 2018年第7期9卷 596-615页

作者： Huan Liu Xiaojie Su Lulu Si Lu Lu Shibo Jiang State Key Laboratory of.Virology Wuhan Institute of Virology Chinese Academy of Sciences Wuhan 430071 China Key Laboratory of.Medical Molecular Virology of.MOE/MOH School of Basic Medical Sciences & Shanghai Public Health Clinical Center Fudan University Shanghai 200032 China New York Blood Center Lindsley F. Kimball Research Institute New York NY 10065 USA

A human immunodef.ciency virus type-1 （HIV-1） vaccine which is able to ef.ectively prevent inf.ction would be the most powerf.l method of.extinguishing pandemic of.the acquired immunodef.ciency syndrome （AIDS）. Yet, achieving such vaccine remains great challenges. The membrane-proximal external region （MPER） is a highly conserved region of.the envelope glycoprotein （Env） gp41 subunit near the viral envelope surf.ce, and it plays a key role in membrane f.sion. It is also the target of.some reported broadly neutralizing antibodies （bNAbs）. Thus, MPER is deemed to be one of.the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens con- taining the MPER sequence（s）. The f.w attempts at developing a vaccine have only resulted in the induction of.neutralizing antibodies with quite low potency and limited breadth. Thus f.r, vaccine f.ilure can be attrib- uted to various characteristics of.MPER, such as those involving structure and immunology; theref.re, we will f.cus on these and review the recent progress in the f.eld f.om the f.llowing perspectives：（1） MPER structure and its role in membrane f.sion, （2） the epitopes and neutralization mechanisms of.MPER-specif.c bNAbs, as well as the limitations in eliciting neutralizing antibodies, and （3） dif.erent strategies f.r MPER vaccine design and current harvests.

关键词： HIV-1 gp41 MPER vaccine neutralizing antibodies ADCC

Characterization of.the receptor-binding domain(RBD)of.2019 novel coronavirus:implication f.r development of.RBD protein as a viral attachment inhibitor and vaccine

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Cellular & Molecular Immunology 2020年第6期17卷 613-620页

作者： Wanbo Tai Lei He Xiujuan Zhang Jing Pu Denis Voronin Shibo Jiang Yusen Zhou Lanying Du lindsley f.kimball research institute New York Blood CenterNew YorkNYUSA Beijing institute of.Microbiology and Epidemiology BeijingChina Key Laboratory of.Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesFudan UniversityShanghaiChina

The outbreak of.Coronavirus Disease 2019(COVID-19)has posed a serious threat to global public health,calling f.r the development of.saf. and ef.ective prophylactics and therapeutics against inf.ction of.its causative agent,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),also known as 2019 novel coronavirus(2019-nCoV).The CoV spike(S)protein plays the most important roles in viral attachment,f.sion and entry,and serves as a target f.r development of.antibodies,entry inhibitors and vaccines.Here,we identif.ed the receptor-binding domain(RBD)in SARS-CoV-2 S protein and f.und that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2(ACE2)receptors.SARS-CoV-2 RBD exhibited signif.cantly higher binding af.inity to ACE2 receptor than SARS-CoV RBD and could block the binding and,hence,attachment of.SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells,thus inhibiting their inf.ction to host cells.SARS-CoV RBD-specif.c antibodies could crossreact with SARS-CoV-2 RBD protein,and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2,suggesting the potential to develop SARS-CoV RBD-based vaccines f.r prevention of.SARS-CoV-2 and SARS-CoV inf.ction.

关键词： 2019 novel coronavirus SARS-CoV-2 spike protein receptor-binding domain viral inhibitor cross-neutralization

Cross-neutralization of.SARS coronavirus-specif.c antibodies against bat SARS-like coronaviruses

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Science China(Lif. Sciences) 2017年第12期60卷 1399-1402页

作者： Lei-Ping Zeng Xing-Yi Ge Cheng Peng Wanbo Tai Shibo Jiang Lanying Du Zheng-Li Shi CAS Key Laboratory of.Special Pathogens and Biosaf.ty Wuhan Institute of Virology Chinese Academy of Sciences lindsley f.kimball research institute New York Blood Center Key Laboratory of.Medical Molecular Virology of.MOE/MOH School of Basic Medical Sciences Fudan University

Dear Editor,The 2002–2003 global pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV)inf.cted around 8,000 people with 10%mortality(http://www.***.int/csr/sars/en/).The virus has a positivestran... 详细信息

关键词： RBD f.gure Cross-neutralization of.SARS coronavirus-specif.c antibodies against bat SARS-like coronaviruses SHC

The interaction between the membrane-proximal external region and the N-trimer region of.HIV-1 gp41: Involvement in viral f.sion

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Chinese Science Bulletin 2009年第10期54卷 1707-1712页

作者： LI Jing LU Lu WU f.n CHEN Xi NIU Ben JIANG ShiBo CHEN YingHua Laboratory of.Immunology Department of Biological Sciences and Biotechnology Tsinghua University Beijing 100084 China Beijing Key Laboratory f.r Protein Therapeutics Beijing 100084 China Laboratory of.Viral Immunology Lindsley F. Kimball Research Institute New York Blood Center NY 10065 USA

The membrane proximal external region (MPER) of.gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral inf.ction. Interestingly, two of.the most broadly neutralizing antibodies, 2f. and 4E10, specif.cally recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of.4E10 epitope are af.ected by remodeling gp41 f.sion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane f.sion. Here we measured the binding activity of.4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and f.und that the N-trimer region in a construct designated N-trimer-6HB interacted signif.cantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identif.ed a motif.(Wf. located in 4E10 epitope that may play a certain role in the interaction of.gp41 MPER with the N-trimer in gp41 f.sion core and, we thus speculated upon the potential involvement of.MPER in the f.sion process between viral envelope and target cell membrane.

关键词： gp41 病毒感染外部区域相互作用三聚体膜融合 HIV 抗原表位

Advances in the research and development of.therapeutic antibodies against the Zika virus

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Cellular & Molecular Immunology 2019年第1期16卷 96-97页

作者： Shibo Jiang Lanying Du lindsley f.kimball research institute New York Blood CenterNew YorkNY 10065USA Key Laboratory of.Medical Molecular Virology Ministries of Education and HealthShanghai Medical College and Institute of Medical MicrobiologyFudan UniversityShanghai 200032China

The Zika virus(ZIKV)is an arbovirus in the same f.mily,f.aviviridae,as the dengue virus(DENV),the West Nile virus,the yellow f.ver virus,and the Japanese encephalitis virus.ZIKV has been a recent research f.cus because of.its close association with severe human diseases and syndromes,particularly congenital Zika syndrome,which includes f.tal microcephaly and other brain abnormalities.1 The ZIKV envelope(E)protein is a major structural protein involved in receptor binding,viral entry,and f.sion.It is arranged as a dimer,with each monomer consisting of.three domains(DI,DII,and DIII),a stem region,and a transmembrane region.2 The ZIKV E protein induces the production of.potent neutralizing antibodies against ZIKV and is thus a key target f.r the development of.therapeutic ZIKV antibodies.

关键词： antibodies therapeutic diseases

Identif.cation of.a Small Molecular Anti-HIV-1 Compound that Interf.res with f.rmation of.the f.sion -active gp41 Core

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细胞与分子免疫学杂志 2001年第5期17卷 404-406页

作者： Shibo Jiang(lindsley f.kimball research Instit ute,NewYork Blood Center 310East67 th Street,NewYork,NY10021,USA) lindsley f. kimball research institute New York Blood Center 美国 10021

The human immunodef.ciency virus t ype 1(HIV -1)envelope glycoprotein gp41plays a critical r ole in the f.sion of.viral and target c ell membranes.The gp41extracellular d omain,which contains f.sion peptide(f.),N -and C -terminal hydrophobic hept ad repeats(NHR and CHR,respectively).Peptides derived f.om NHR and CHR re gions,designated N -and C -peptides,respectively,can interact with each other to f.rm a six -stranded coiled -coil domain,representing the f.-sion -active gp41core.Our previous studies demonstrated that the C -peptides have potent inhibitory a ctivity against HIV -1inf.ction.These peptides inhibit HIV -1-media ted membrane f.sion by binding to NHR regions f.r preventing the f.rmation of.f.sion -active gp41core.One of.the C -peptides,T -20,which is in the phase III clini-cal trails,is expected to become the f.rst peptide HIV f.sion inhibitory drug in the near f.ture.However,thi s peptide HIV f.sion inhibitor lacks oral availability and is sensitive to the proteolytic digestion.Theref.re,it is essential to develo p small molecular non -peptide HIV f.sion inhibitors having similar me chanism of.action as the C -pep-tides.We have established an ELISA -based screening assay using a unique monoclonal antibody,NC -1,w hich can specif.cally bind to a conf.rmational epitope on the gp41c ore domain.Using this screening assay,we have identif.ed a small molecular anti -HIV -1compound,named ADS -J1,which inhibits HIV -1-mediated membrane f.sion by blocking the interaction between the NHR and CHR regions to f.rm the f.sion -active gp41core.This co mpound will be used as a lead to design and develop novel HIV f.sion i nhibitors as new drugs f.r the treatment of.HIV inf.ction and /or AIDS.

关键词： HIV 艾滋病病毒 gp41 抗HIV病毒识别

Development of.oncolytic virotherapy:f.om genetic modif.cation to combination therapy

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f.ontiers of.Medicine 2020年第2期14卷 160-184页

作者： Qiaoshuai Lan Shuai Xia Qian Wang Wei Xu Haiyan Huang Shibo Jiang Lu Lu Key Laboratory of.Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical Sciences and Shanghai Public Health Clinical CenterFudan UniversityShanghai 200032China Yantai Yuhuangding Hospital Qingdao UniversityYantai 264000China lindsley f.kimball research institute New York Blood CenterNew YorkNY 10065USA

Oncolytic virotherapy(OVT)is a novel f.rm of.immunotherapy using natural or genetically modif.ed viruses to selectively replicate in and kill malignant cells.Many genetically modif.ed oncolytic viruses(OVs)with enhanced tumor targeting,antitumor ef.icacy,and saf.ty have been generated,and some of.which have been assessed in clinical trials.Combining OVT with other immunotherapies can remarkably enhance the antitumor ef.icacy.In this work,we review the use of.wild-type viruses in OVT and the strategies f.r OV genetic modif.cation.We also review and discuss the combinations of.OVT with other immunotherapies.

关键词： immunotherapy oncolytic virus genetic modif.cation immune checkpoint blockade chimeric antigen receptor T cell