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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 | Characterization of the receptor-binding domain(RBD)of 2019 novel coronavirus:implication for development of RBD protein as a viral attachment inhibitor and vaccine显示文摘The outbreak of Coronavirus Disease 2019(COVID-19)has posed a serious threat to global public health,calling for the development of safe and effective prophylactics and therapeutics against infection 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,fusion and entry,and serves as a target for development of antibodies,entry inhibitors and vaccines.Here,we identified the receptor-binding domain(RBD)in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2(ACE2)receptors.SARS-CoV-2 RBD exhibited significantly higher binding affinity 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 infection to host cells.SARS-CoV RBD-specific 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 for prevention of SARS-CoV-2 and SARS-CoV infection. | Wanbo Tai Lei He Xiujuan Zhang Jing Pu Denis Voronin Shibo Jiang Yusen Zhou Lanying Du | 2020 | Cellular & Molecular Immunology2020,17,6: | 35 |
| 4 | A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome显示文摘By the end of 2019,the World Health Organization(WHO)was informed about an outbreak of pneumonia of unknown etiology in Wuhan,China.Some patients were linked to a seafood market,suggesting animal-to-human transmission,but,soon,human-tohuman transmission was confirmed.The pathogen was promptly identified as a novel coronavirus belonging to lineage B betacoronaviruses that also include severe acute respiratory syndrome coronavirus(SARS-CoV),which caused a pandemic in China in 2002/2003,and bat SARS-like coronaviruses. | Shibo Jiang Shuai Xia Tianlei Ying Lu Lu | 2020 | Cellular & Molecular Immunology2020,17,5: | 33 |
| 5 | 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 |
| 6 | Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus显示文摘 | Naru Zhang Rudragouda Channappanavar Cuiqing Ma Lili Wang Jian Tang Tania Garron Xinrong Tao Sumaiya Tasneem Lu Lu Chien-Te K Tseng Yusen Zhou Stanley Perlman Shibo Jiang Lanying Du | 2016 | Cellular & Molecular Immunology2016,13,2: | 12 |
| 7 | The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus显示文摘Based on the announcement of the World Health Organization(WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus(SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate(R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as 'transmissible acute respiratory syndrome coronavirus(TARS-CoV)' and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain(RBD) and viral fusion inhibitors targeting the heptad repeat 1(HR1) domain in spike protein of 2019-nCoV. | Shibo Jiang Zheng-Li Shi | 2020 | Virologica Sinica2020,35,3: | 11 |
| 8 | A novel strategy for rapid construction of libraries of full-length antibodies highly expressed on mammalian cell surfaces显示文摘一个万用的哺乳动物的显示器系统的开发为有高亲密关系的功能的人的抗体的选择是必要的。这里,我们为能高效地在哺乳动物的房间表面上被表示的全身的抗体图书馆的快速的建设描述了新奇策略。通用向量 pDGB-HC-TM 被插入唯一的序列为兴趣的基因的突然发生在里面和突然发生外面由限制 endonucleases BsmBI, SfiI,和 BstXI 认出了的多重克隆的地点构造。 Cytomegalovirus 倡导者,为在许多哺乳动物的房间的蛋白质的高表示的一个通常使用的倡导者,被用来从导出血小板的生长驾驶插入的抗体基因和一个 transmembrane 领域的表示因素受体在框架被熔化到重链的C终点一致区域到抗体在哺乳动物的房间表面上表示了的锚。用这策略,我们构造了一个全身的人的抗体显示图书馆。DNA 顺序分析和表示分析显示图书馆构造了有 6.58 e 的组合可表现的、可检测的差异 ???汩 l 吗?? | Ye Zhou Zhen-Rui Chen Chang-Zheng Li Wei He Shuwen Liu Shibo Jiang Wen-Li Ma Wanlong Tan Chen Zhou | 2010 | Acta Biochimica et Biophysica Sinica2010,42,8: | 11 |
| 9 | 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 |
| 10 | 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 |
| 11 | Identification of HBsAg-specific antibodies from a mammalian cell displayed full-length human antibody library of healthy immunized donor显示文摘肝炎 B 免疫球蛋白(HBIG ) 在肝炎 B 的管理是重要的病毒(HBV ) 感染。试图作为 HBIG 的一种选择开发 recombinant monoclonal 抗体,我们报导 HBV 表面抗原(HBsAg ) 的成功的鉴定从在哺乳动物的房间上显示的一个全身的人的抗体图书馆的特定的抗体出现。把一个生来地使免疫的施主的外部血 mononuclear 房间的全部的 RNA 用作模板,抗体全部剧目被放大。联合四方法的结扎和 Flp 调停 recombinase 的集成(Flp 在里面) 系统,我们构造了每个房间在显示了一个种仅仅抗体分子的一个哺乳动物的基于房间的、充分人的、全身的抗体显示图书馆。由屏蔽使用激活荧光的房间排序的房间图书馆(FACS ) ,八个房间克隆显示那房间表面上的 HBsAg 特定的抗体被识别。抗体基因的 DNA 顺序分析揭示了三唯一的抗体。FACS 数据显示了那荧光灯表示(FSE ) 的力量,荧光灯绑定(FSB ) 的力量和相对有约束力的能力(RBA ) 都在他们之中是不同的。这些结果由使用我们的抗体表明了那哺乳动物的显示和屏蔽站台,我们能成功地从一个使免疫的全身的抗体图书馆识别抗原特定的抗体。因此,这个平台为治疗学的抗体的开发是很有用的。 | Chang-Zheng Li Zhong-Kun Liang Zhen-Rui Chen Hai-Bo Lou Ye Zhou Zhe-Huan Zhang Fei Yu Shuwen Liu Yuanping Zhou Shuguang Wu Wenling Zheng Wanlong Tan Shibo Jiang Chen Zhou | 2012 | Cellular & Molecular Immunology2012,9,2: | 7 |
| 12 | Four-way ligation for construction of a mammalian cell-based full-length antibody display library显示文摘唯一的四方法的结扎策略为一个全身的抗体图书馆的快速的建设被开发。哺乳动物的表示向量被构造盒子和序列由唯一的限制酶 BsmBI, BstXI,和 SfiI 认出了的那包含的双哺乳动物的表情。重链的基因的全身的轻链、可变的领域被四方法的结扎在一步插入到向量,并且全身的二原子价的抗体在哺乳动物的房间表面上被显示。用这策略,仅仅 2 个星期被要求成功地构造高质量的、全身的人的抗体图书馆。 | Ivan Zhou Zhe-Huan Zhang Chang-Zheng Li Zhen-Rui Chen Wei He Ye Zhou Shuwen Liu Shuguang Wu Yuanping Zhou Wanlong Tan Shibo Jiang Chen Zhou | 2011 | Acta Biochimica et Biophysica Sinica2011,43,3: | 6 |
| 13 | Roles of the hemagglutinin of influenza A virus in viral entry and development of antiviral therapeutics and vaccines显示文摘Seasonal influenza epidemics and influenza pandemics caused by influenza A virus(IAV)has resulted in millions of deaths in the world.The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics.Hemagglutinin(HA)of IAV plays a critical role in viral binding,fusion and entry,and contains the major neutralizing epitopes.Therefore,HA is an attractive target for developing anti-IAV drugs and vaccines.Here we have reviewed the recent progress in study of conformational changes of HA during viral fusion process and development of HA-based antiviral therapeutics and vaccines. | Shibo Jiang Runming Li Lanying Du Shuwen Liu | 2010 | Protein & Cell2010,1,4: | 5 |
| 14 | 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 |
| 15 | A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2显示文摘Dear Editor,The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)highlights the need to develop effective and safe vaccines.Similar to SARS-CoV,SARS-CoV-2 recognizes angiotensin-converting enzyme 2(ACE2)as receptor for host cell entry.1,2 SARS-CoV-2 spike(S)protein consists of S1,including receptor-binding domain(RBD),and S2 subunits.3,4 We previously demonstrated that RBDs of SARS-CoV and MERS-CoV serve as important targets for the development of effective vaccines. | Wanbo Tai Xiujuan Zhang Aleksandra Drelich Juan Shi Jason CHsu Larry Luchsinger Christopher D.Hillyer Chien-Te KTseng Shibo Jiang Lanying Du | 2020 | Cell Research2020,30,10: | 5 |
| 16 | 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 |
| 17 | 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 |
| 18 | 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 |
| 19 | 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 |
| 20 | 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 |