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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 | 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 |
| 3 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | 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 |
| 8 | 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 |
| 9 | A core epitope targeting antibody of SARS-CoV-2显示文摘Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes. | Simeng Zhao Fengjiang Liu Shizhen Qiu Qiaoshuai Lan Yiran Wu Wei Xu Junzi Ke Jie Yang Xiaoyan Liu Kun Wang Hangtian Guo Shuai Xia Fangfang Zhang Jiabei Wang Xiaowen Hu Lu Lu Shibo Jiang Suwen Zhao Lianxin Liu Youhua Xie Xiuna Yang Haopeng Wang Guisheng Zhong | 2023 | Protein & Cell2023，14，1： | 0 |
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