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| 1 | Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion显示文摘The recent outbreak of coronavirus disease(COVID-19)caused by SARS-CoV-2 infection in Wuhan,China has posed a serious threat to global public health.To develop specific anti-coronavirus therapeutics and prophylactics,the molecular mechanism that underlies viral infection must first be defined.Therefore,we herein established a SARS-CoV-2 spike(S)protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV.We solved the X-ray crystal structure of six-helical bundle(6-HB)core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain.We previously developed a pan-coronavirus fusion inhibitor,EK1,which targeted the HR!domain and could inhibit infection by divergent human coronaviruses tested,including SARS-CoV and MERS-CoV.Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM,about 241-and 149-fold more potent than the original EK1 peptide,respectively.EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested,including SARS-CoV and MERS-CoV,as well as SARSr-CoVs,and potently inhibited the replication of 5 live human coronaviruses examined,including SARS-CoV-2.Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection,suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs. | Shuai Xia Meiqin Liu Chao Wang Wei Xu Qiaoshuai Lan Siliang Feng Feifei Qi Linlin Bao Lanying Du Shuwen Liu Chuan Qin Fei Sun Zhengli Shi Yun Zhu Shibo Jiang Lu Lu | 2020 | Cell Research2020，30，4： | 81 |
| 2 | AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells显示文摘The current coronavirus disease 2019(COVID-19)pandemic presents a global public health challenge.The viral pathogen responsible,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),binds to the host receptor ACE2 through its spike(S)glycoprotein,which mediates membrane fusion and viral entry.Although the role of ACE2 as a receptor for SARS-CoV-2 is clear,studies have shown that ACE2 expression is extremely low in various human tissues,especially in the respiratory tract.Thus,other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist.In this study,we found that the tyrosine-protein kinase receptor UFO(AXL)specifically interacts with the N-terminal domain of SARS-CoV-2 S.Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2,we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2,while knocking out AXL significantly reduces SARS-CoV-2 infection in HI 299 pulmonary cells and in human primary lung epithelial cells.Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL.The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients.Taken together,our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies. | Shuai Wang Zongyang Qiu Yingnan Hou Xiya Deng Wei Xu Tingting Zheng Peihan Wu Shaofang Xie Weixiang Bian Chong Zhang Zewei Sun Kunpeng Liu Chao Shan Aifu Lin Shibo Jiang Youhua Xie Qiang Zhou Lu Lu Jing Huang Xu Li | 2021 | Cell Research2021，31，2： | 39 |
| 3 | Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein显示文摘Very recently,a novel coronavirus,2019-nCoV,emerged in Wuhan,China and then quickly spread worldwide,resulting in>17,388 confirmed cases and 361 deaths as of 3 February 2020,thus calling for the development of safe and effective therapeutics and prophylatics.1,2 Similar to severe acute respiratory syndrome(SARS)-CoV,2019-nCoV belongs to lineage B betacoronavirus,and it has the ability to utilize human angiotensin-converting enzyme 2(ACE2)as a receptor to infect human cells. | Shuai Xia Yun Zhu Meiqin Liu Qiaoshuai Lan Wei Xu Yanling Wu Tianlei Ying Shuwen Liu Zhengli Shi Shibo Jiang Lu Lu | 2020 | Cellular & Molecular Immunology2020，17，7： | 27 |
| 4 | The role of furin cleavage site in SARS-CoV-2 spike protein-mediated membrane fusion in the presence or absence of trypsin显示文摘Dear Editor,The rapid spread of SARS-CoV-2(also known as 2019-nCoV and HCoV-191),a novel lineage B betacoronavirus(βCoV),has caused a global pandemic of coronavirus disease(COVID-19).It has been speculated that RRAR,a unique furin-like cleavage site(FCS)in the spike protein(S),which is absent in other lineage BβCoVs,such as SARS-CoV,is responsible for its high infectivity and transmissibility. | Shuai Xia Qiaoshuai Lan Shan Su Xinling Wang Wei Xu Zezhong Liu Yun Zhu Qian Wang Lu Lu Shibo Jiang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 8 |
| 5 | RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response显示文摘The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed serious threats to global health and economy,thus calling for the development of safe and effective vaccines.The receptorbinding domain(RBD)in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2(ACE2)receptor.It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines.Here,we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG,as an immunopotentiator,elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections.The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus(SARSr-CoV).Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge.These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants,as well as future emerging SARSr-CoVs and re-emerging SARS-CoV. | Zezhong Liu Wei Xu Shuai Xia Chenjian Gu Xinling Wang Qian Wang Jie Zhou Yanling Wu Xia Cai Di Qu Tianlei Ying Youhua Xie Lu Lu Zhenghong Yuan Shibo Jiang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 6 | Salvianolic acid C potently inhibits SARS-CoV-2 infection by blocking the formation of six-helix bundle core of spike protein显示文摘Dear Editor,The pandemic of COVID-19 caused by SARS-CoV-2 infection has posed a serious threat to global public health and the economy.Up to now,although several potentially effective antiviral drugs are under evaluating in clinical trials around the world,1 there are still no specific antiviral countermeasures beyond supportive therapies have been established.We herein report that the hydrophilic compound Salvianolic acid C(Sal-C)from Danshen,a traditional Chinese medicine(TCM),potently inhibit SARS-CoV-2 infection by blocking the formation of six-helix bundle(6-HB)core of spike(S)protein. | Chan Yang Xiaoyan Pan Xinfeng Xu Chen Cheng Yuan Huang Lin Li Shibo Jiang Wei Xu Gengfu Xiao Shuwen Liu | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 5 |
| 7 | A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice,rabbits and NHPs显示文摘The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines.Here,we discovered a new STING agonist,CF501,and found that CF501-adjuvanted RBD-FC vaccine(CF501/RBD-FC)elicited significantly stronger neutralizing antibody(nAb)and T cell responses than Alum-and cGAMP-adjuvanted RBD-FC in mice.Vaccination of rabbits and rhesus macaques(nonhuman primates,NHPs)with CF501/RBD-FC elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants,SARS-CoV and bat SARSr-CoVs.CF501/RBD-FC-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge,even 6 months after the initial immunization.NHPs immunized with a single dose of CF501/RBD-FC produced high titers of nAbs.The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization.Thus,CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases. | Zezhong Liu Jie Zhou Wei Xu Wei Deng Yanqun Wang Meiyu Wang Qian Wang Ming Hsieh Jingming Dong Xinling Wang Weijin Huang Lixiao Xing Miaoling He Chunlin Tao Youhua Xie Yilong Zhang Youchun Wang Jincun Zhao Zhenghong Yuan Chuan Qin Shibo Jiang Lu Lu | 2022 | Cell Research2022，32，3： | 5 |
| 8 | A highly potent and stable pan-coronavirus fusion inhibitor as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases显示文摘The development of broad-spectrum antivirals against human coronaviruses(HCoVs)is critical to combat the current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,as well as future outbreaks of emerging CoVs.We have previously identified a polyethylene glycol-conjugated(PEGylated)lipopeptide,EK1C4,with potent pan-CoV fusion inhibitory activity.However,PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo.Therefore,we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment(HR2-CF)of HCoV-OC43.Among these lipopeptides,EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike(S)mutants,as well as other HCoVs and some bat SARS-related coronaviruses(SARSr-CoVs)tested.The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes,better metabolic stability in mouse serum,higher thermostability than the PEGylated lipopeptide EK1C4,suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases. | Jie Zhou Wei Xu Zezhong Liu Chao Wang Shuai Xia Qiaoshuai Lan Yanxing Cai Shan Su Jing Pu Lixiao Xing Youhua Xie Lu Lu Shibo Jiang Qian Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 5 |
| 9 | Engineered trimeric ACE2 binds viral spike protein and locks it in'Thfee-up'conformation to potently inhibit SARS-CoV-2 infection显示文摘Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in a severe global pandemic Following SARS-CoV,SARS-CoV-2 is yet another emerge nt beta-coronavirus threate ning human health.1 However,seventeen years after the SARS pandemic,no targeted vaccines or therapeutics have been approved for SARS,while some of them might have held promise for treating COVID-19.Many neutralizing antibodies against SARS-CoV-2 are currently being developed.However,RNA viruses are known to have high mutation rates. | Liang Guo Wenwen Bi Xinling Wang Wei Xu Renhong Yan Yuanyuan Zhang Kai Zhao Yaning Li Mingfeng Zhang Xia Cai Shibo Jiang Youhua Xie Qiang Zhou Lu Lu Bobo Dang | 2021 | Cell Research2021，31，1： | 5 |
| 10 | Retraction Note to:SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion显示文摘The authors have retracted this article1.After the publication of this article,it came to the authors attention that in order to support the conclusions of the study,the authors should have used primary T cells instead of T-cell lines.In addition,there are concerns that the flow cytometry methodology applied here was flawed.These points resulted in the conclusions being considered invalid. | Xinling Wang Wei Xu Gaowei Hu Shuai Xia Zhiping Sun Zezhong Liu Youhua Xie Rong Zhang Shibo Jiang Lu Lu | 2020 | Cellular & Molecular Immunology2020，17，8： | 5 |
| 11 | Griffithsin with A Broad-Spectrum Antiviral Activity by Binding Glycans in Viral Glycoprotein Exhibits Strong Synergistic Effect in Combination with A Pan-Coronavirus Fusion Inhibitor Targeting SARS-CoV-2 Spike S2 Subunit显示文摘Dear Editor,The pandemic of coronavirus disease 2019(COVID-19)caused by SARS-Co V-2 has posed a significant threat to global public health and economy,thus calling for the rapid development of effective therapeutics and prophylactics.Repurposing existing medicines with clinical safety profiles offers a more rapid hope of combating COVID-19pandemic than developing a new therapeutic. | Yanxing Cai Wei Xu Chenjian Gu Xia Cai Di Qu Lu Lu Youhua Xie Shibo Jiang | 2020 | Virologica Sinica2020，35，6： | 4 |
| 12 | A pan-sarbecovirus vaccine induces highly potent and durable neutralizing antibody responses in non-human primates against SARS-CoV-2 Omicron variant显示文摘Dear Editor,Since the outbreak of Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,numerous SARS-CoV-2 variants of concern(VOCs),such as Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),and Delta(B.1.617.2),have emerged.Recently,the newly identified SARS-CoV-2 VOC,Omicron(B.1.1.529),has rapidly spread in many countries1 and is expected to replace Delta as the dominant variant circulating in the world.Compared to other VOCs,Omicron contains at least 32 mutations in spike(S)protein,including 15 mutations in the receptor-binding domain(RBD),and these mutations are known to confer resistance to neutralizing antibodies(nAbs)and sera of convalescent patients and people who have received COVID-19 vaccines.2–5 Therefore,vaccines able to induce potent and durable neutralizing antibodies against Omicron and other VOCs are urgently needed. | Zezhong Liu Jasper Fuk-Woo Chan Jie Zhou Meiyu Wang Qian Wang Guangxu Zhang Wei Xu Kenn Ka-Heng Chik Yilong Zhang Youchun Wang Kwok-Yung Yuen Lu Lu Shibo Jiang | 2022 | Cell Research2022，32，5： | 4 |
| 13 | Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc显示文摘Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely understood.In this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and metabolism.Genetic ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs metabolism.Sin1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral immunity.At the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,respectively.Therefore,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism. | Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin Yuheng Han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su | 2019 | Cellular & Molecular Immunology2019，16，9： | 4 |
| 14 | Development of oncolytic virotherapy:from genetic modification to combination therapy显示文摘Oncolytic virotherapy(OVT)is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells.Many genetically modified oncolytic viruses(OVs)with enhanced tumor targeting,antitumor efficacy,and safety have been generated,and some of which have been assessed in clinical trials.Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy.In this work,we review the use of wild-type viruses in OVT and the strategies for OV genetic modification.We also review and discuss the combinations of OVT with other immunotherapies. | Qiaoshuai Lan Shuai Xia Qian Wang Wei Xu Haiyan Huang Shibo Jiang Lu Lu | 2020 | Frontiers of Medicine2020，14，2： | 4 |
| 15 | Inefficiency of Sera from Mice Treated with Pseudotyped SARS-CoV to Neutralize 2019-nCoV Infection显示文摘Dear Editor,An outbreak of unusual pneumonia in Wuhan, China recently was caused by infection of a novel type of coronavirus. The virus and disease were denoted as 2019-nCoV and COVID-19, respectively, by the World Health Organization(WHO). Most recently, 2019-nCoV was renamed SARS-CoV-2 by Coronaviridae Study Group(CSG) of the International Committee on Taxonomy of Viruses(ICTV)(Gorbalenya et al. 2020)。 | Zezhong Liu Shuai Xia Xinling Wang Qiaoshuai Lan Wei Xu Qian Wang Shibo Jiang Lu Lu | 2020 | Virologica Sinica2020，35，3： | 3 |
| 16 | Safety and Efficacy of Conbercept in Neovascular Age-Related Macular Degeneration Results from a 12-month Randomized Phase II Study: AURORA Study显示文摘 | Xiaoxin Li Gezhi Xu Yusheng Wang Xun Xu Xiaoling Liu Shibo Tang Feng Zhang Junjun Zhang Luosheng Tang Quan Wu Delun Luo Xiao Ke | 2014 | Ophthalmology2014，，： | 2 |
| 17 | Peptide-based pan-CoV fusion inhibitors maintain high potency against SARS-CoV-2 Omicron variant显示文摘Dear Editor,Most recently,a new SARS-CoV-2 variant of concern(VOC)Z Omicron(B.1.1.529),was first reported to the World Health Organization(WHO)from South Africa and then quickly spread to many countries,1,2 posing a serious threat to current vaccine prevention and antibody therapeutic strategies.Several studies have reported that the Omicron variant successfully escapes from neutralizing antibodies elicited by COVID-19 vaccines or from COVID-19 convalescent patients. | Shuai Xia Jasper Fuk-Woo Chan Lijue Wang Fanke Jiao Kenn Ka-Heng Chik Hin Chu Qiaoshuai Lan Wei Xu Qian Wang Chao Wang Kwok-Yu ng Yuen Lu Lu Shibo Jiang | 2022 | Cell Research2022，32，4： | 2 |
| 18 | Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation显示文摘The COVID-19 pandemic poses a global threat to public health and economy.The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines.In this study,we identified that EK1 and cholesterol-coupled derivative of EK1,EK1C4,as pan-CoV fusion inhibitors,exhibit potent antiviral activity against SARS-CoV-2 infection in both lung-and intestine-derived cell lines(Calu-3 and Caco2,respectively).They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7(Alpha)and B.l.1.248(Gamma)as well as those with mutations in S protein,including N417T,E484K,N501Y,and D614G,which are common in South African and Brazilian variants.Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity.Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues.EK1 showed good safety profiles in various animal models,supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants. | Shuai Xia Qiaoshuai Lan Yun Zhu Chao Wang Wei Xu Yutang Li Lijue Wang Fanke Jiao Jie Zhou Chen Hua Qian Wang Xia Cai Yang Wu Jie Gao Huan Liu Ge Sun Jan Munch Frank Kirchhoff Zhenghong Yuan Youhua Xie Fei Sun Shibo Jiang Lu Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，8： | 2 |
| 19 | Bimodal PE prepared with combined iron (II) and nickel (II) olefin polymerization catalysts显示文摘Combined iron (II) and nickel (II) olefin polymerization catalysts could produce a kind of PE having the characters of ideal bimodal PE with ap- propriate conditions and catalysts. In the ethylene homopolymerization with triethylalkylaluminum (AlEt3) as the activator, the prepared bimodal PE contained not only branched PE of high molecular weight, but also linear PE of low molecular weight. And the amounts of both fractions were similar. Ideal bimodal PE resin was prepared in one polymerization reactor. | WANG Shibo LIU Dongbing XU Renwei MAO Bingquan | 2006 | Chinese Science Bulletin2006，51，1： | 1 |
| 20 | Preparation of spherical MgCl2-supported bis(phenoxy-imine) zirconium complex for ethylene polymerization显示文摘 | Xu Renwei Liu Donghing Wang Shibo | | 0，，： | 1 |
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