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| 1 | Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro显示文摘Dear Editor,In December 2019,a novel pneumonia caused by a previously unknown pathogen emerged in Wuhan,a city of 11 million people in central China.The initial cases were linked to exposures in a seafood market in Wuhan.1 As of January 27,2020,the Chinese authorities reported 2835 confirmed cases in China's Mainland,including 81 deaths.Additionally,19 confirmed cases were identified in Hong Kong,Macao and Taiwan,and 39 imported cases were identified in Thailand,Japan,South Korea,United States,Vietnam,Singapore,Nepal,France,Australia and Canada.The pathogen was soon identified as a novel coronavirus(2019-nCoV),which is closely related to sever acute respiratory syndrome CoV(SARS-CoV).2 Currently,there is no specific treatment against the new virus.Therefore,identifying effective antiviral agents to combat the disease is urgently needed. | Manli Wang Ruiyuan Cao Leike Zhang Xinglou Yang Jia Liu Mingyue Xu Zhengli Shi Zhihong Hu Wu Zhong Gengfu Xiao | 2020 | Cell Research2020，30，3： | 563 |
| 2 | Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide,such as the on-going outbreak of the novel coronavirus SARS-CoV-2.Herein,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 SARS-CoV-2.Notably,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 cells.Our 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 cells.This 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. | 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 | 2020 | Protein & Cell2020，11，10： | 14 |
| 3 | Design and development of an oral remdesivir derivative W116 against SARS-CoV-2显示文摘Dear Editor,Since the declaration of COVID-19 as a global pandemic on March 11,2020,this pandemic has been circulating for 17 months throughout the world,leading to more than 200 million infections and nearly 4.4 million deaths as of August 15,2021.The pathogen of COVID-19 is a novel coronavirus named SARS-CoV-2,which shares-79%genome sequence identity with SARS-CoV.1 At the early stage of the COVID-19 outbreak,5ARS-CoV-2 caused great panic in the hardest-hit areas due to its high transmissibility and pathogenicity.To fight the COVID-19 crisis,drug repurposing was immediately pursued in order to find potential therapeutics. | Yuanchao Xie Wanchao Yin Yumin Zhang Weijuan Shang Zhen Wang Xiaodong Luan Guanghui Tian Haji A.Aisa Yechun Xu Gengfu Xiao Jia Li Hualiang Jiang Shuyang Zhanq Leike Zhang H.Eric Xu Jingshan Shen | 2021 | Cell Research2021，31，11： | 12 |
| 4 | Isolation and characterization of Zika virus imported to China using C6/36 mosquito cells显示文摘Dear Editor,Zika virus(ZIKV)is a mosquito-borne flavivirus that usually causes asymptomatic infections or mild illness in humans.However,the unprecedented epidemics of ZIKV in Latin America since early 2015 have made this flavivirus an international health risk(Liu and Zhang,2016).In particular,the potential association of ZIKV infection with the remarkable increase in the number | Chenglin Deng Siqing Liu Qiuyan Zhang Mingyue Xu Honglei Zhang Dayong Gu Lei Shi Jian'an He Gengfu Xiao Bo Zhang | 2016 | Virologica Sinica2016，31，2： | 12 |
| 5 | SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target显示文摘Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death.However,the origin of excessive damages caused by SARS-CoV-2 remains largely unknown.Here we show that the SARS-CoV-2 envelope(2-E)protein alone is able to cause acute respiratory distress syndrome(ARDS)-like damages in vitro and in vivo. | Bingqing Xia Xurui Shen Yang He Xiaoyan Pan Feng-Liang Liu Yi Wang Feipu Yang Sui Fang Yan Wu Zilei Duan Xiaoli Zuo Zhuqing Xie Xiangrui Jiang Ling Xu Hao Chi Shuangqu Li Qian Meng Hu Zhou Yubo Zhou Xi Cheng Xiaoming Xin Lin Jin Hai-Lin Zhang Dan-Dan Yu Ming-Hua Li Xiao-Li Feng Jiekai Chen Hualiang Jiang Gengfu Xiao Yong-Tang Zheng Lei-Ke Zhang Jingshan Shen Jia Li Zhaobing Gao | 2021 | Cell Research2021，31，8： | 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 | Total Chemical Synthesis, Assembly of Human Torque Teno Virus Genome显示文摘Torque teno virus(TTV) is a nonenveloped virus containing a single-stranded,circular DNA genome of approximately 3.8kb.We completely synthesized the 3 808 nucleotides of the TTV(SANBAN isolate) genome,which contains a hairpin structure and a GC-rich region.More than 100 overlapping oligonucleotides were chemically synthesized and assembled by polymerase chain assembly reaction(PCA),and the synthesis was completed with splicing by overlap extension(SOEing).This study establishes the methodological basis of the chemical synthesis of a viral genome for use as a live attenuated vaccine or gene therapy vector. | Zheng Hou Gengfu Xiao | 2011 | Virologica Sinica2011，26，3： | 4 |
| 8 | SECONDARY INSTABILITY WITH RESPECT TO SPATIAL GROWING THREE-DIMENSIONAL SUBHARMONIC DISTURBANCES IN BOUNDARY LAYER FLOW WITH SUCTION显示文摘SECONDARYINSTABILITYWITHRESPECTTOSPATIALGROWINGTHREE-DIMENSIONALSUBHARMONICDISTURBANCESINBOUNDARYLAYERFLOWWITHSUCTION￥ZhaoGen... | Zhao, Gengfu | 1995 | Journal of Hydrodynamics1995，7，3： | 4 |
| 9 | Structure-function relationship of the mammarenavirus envelope glycoprotein显示文摘Mammarenaviruses, including lethal pathogens such as Lassa virus and Junín virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein(GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex(GPC) formed by a stable signal peptide(SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity. GP1 is responsible for binding to the cell receptor, and GP2 is a class I fusion protein. The native structure of the tripartite GPC is unknown.GPC is critical for the receptor binding, membrane fusion and neutralization antibody recognition.Elucidating the molecular mechanisms underlining the structure–function relationship of the three subunits is the key for understanding their function and can facilitate novel avenues for combating virus infections. This review summarizes the basic aspects and recent research of the structure–function relationship of the three subunits. We discuss the structural basis of the receptor-binding domain in GP1, the interaction between SSP and GP2 and its role in virion maturation and membrane fusion, as well as the mechanism by which glycosylation stabilizes the GPC structure and facilitates immune evasion. Understanding the molecular mechanisms involved in these aspects will contribute to the development of novel vaccines and treatment strategies against mammarenaviruses infection. | Wei Wang Zheng Zhou Leike Zhang Shaobo Wang Gengfu Xiao | 2016 | Virologica Sinica2016，31，5： | 4 |
| 10 | Conformational conversion of prion protein in prion diseases显示文摘Prion 疾病是一组传染致命的 neurodegenerative 疾病。进反常错误褶层 isoform (PrPSc ) 的细胞的 prion 蛋白质(PrPC ) 的 conformational 变换是在 prion 疾病病理的关键事件。在正常条件下面,高精力的障碍把 PrPC 与 PrPSc isoform 分开。然而,病原的变化,修正以及一些余因子例如 glycosaminoglycans, nucleic 酸,和类脂化合物,能调制 conformational 变换过程。理解 prion 蛋白质的 conformational 变换的机制为生物医学的研究和 prion 疾病的治疗是必要的。特别地,与 prion 蛋白质交往的余因子的描述可能提供新诊断、治疗学的策略。 | Zheng Zhou Gengfu Xiao | 2013 | Acta Biochimica et Biophysica Sinica2013，45，6： | 4 |
| 11 | High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors显示文摘A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three'hot'spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments. | Yao Zhao Xiaoyu Du Yinkai Duan Xiaoyan Pan Yifang Sun Tian You Lin Han Zhenming Jin Weijuan Shang Jing Yu Hangtian Guo Qianying Liu Yan Wu Chao Peng Jun Wang Chenghao Zhu Xiuna Yang Kailin Yang Ying Lei Luke W.Guddat Wenqing Xu Gengfu Xiao Lei Sun Leike Zhang Zihe Rao Haitao Yang | 2021 | Protein & Cell2021，12，11： | 4 |
| 12 | Comprehensive interactome analysis of the spike protein of swine acute diarrhea syndrome coronavirus显示文摘Swine acute diarrhea syndrome coronavirus(SADS‐CoV)is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets.SADS‐CoV was reported to be capable of infecting cell lines derived from diverse species,including bats,mice,hamsters,rats,chickens,pigs,nonhuman primates,and humans,implying its high risk of cross‐species infection.However,its receptor is still unknown.In this study,the receptor‐binding domain of the SADS‐CoV spike(S)protein was purified and then subjected to affinity purification(AP)‐coupled mass spectrometry(MS)‐based proteomic analysis to identify the interactors of the SADS‐CoV S protein.Forty‐three host proteins were identified,and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as“cell‐cell adhesion”,“translation”“viral transcription”,suggesting that these processes may participate in the SADS‐CoV life cycles.RNA interference‐based screening of these interactors indicated that PPIB and vimentin can affect SADS‐CoV replication.Our study provides an overarching view into the host interactome of the SADS‐CoV S protein and highlights potential targets for the development of therapeutics against SADS‐CoV. | Qingxing Wang Yun Luo Weijuan Shang Zhengli Shi Gengfu Xiao Leike Zhang | 2021 | Biosafety and Health2021，3，3： | 3 |
| 13 | Bioinformatics analysis on ORFl protein of Torque teno virus(SANBAN isolate)显示文摘Objective:To analyze the sequence of ORFl protein of Torque teno virus to prepare for the future hyhrid experiments.Methods:The sequence of ORFl protein of Torque teno vims was analyzed by bioinformalics using some web lools.Results:The most likely cleavage site was between position 14aa and 15aa and signal peptide may be position laa-14aa.Two possible transmembrane helices from inside to outside and three possible transmembrane helices from outside to inside were found.The position 509(NKTN) was the potential:V-glyeosylation site. The speculative molecular weight of TTV ORF1 protein,which may be a kind of unstable protein was 88 705.7 Da.laa-91aa and 278aa-361aa were localized in non-regular secondary structure region.Conclusions:TTV ORF1 protein may be a nuclear protein which contains two nonregular secondary structure region.265aa to 486aa and 510aa to 679aa may be the two approciale fragments to construct the plasmids,which would be prepared for the future hybrid experiments to study the functional positions of the protein and the interactions between TTV and its hosts. Bioinformatics analysis would possibly make it easier to study the protein’s function. | Chen Jinling Zhu Dandan Shen Pei Sun Wei Xiao Gengfu Duan Yinong Zhu Ying | 2011 | Asian Pacific Journal of Tropical Medicine2011，4，11： | 3 |
| 14 | Assembly of long DNA sequences using a new synthetic Escherichia coli-yeast shuttle vector显示文摘Synthetic biology is a newly developed field of research focused on designing and rebuilding novel biomolecular components, circuits, and networks. Synthetic biology can also help understand biological principles and engineer complex artificial metabolic systems. DNA manipulation on a large genome-wide scale is an inevitable challenge, but a necessary tool for synthetic biology. To improve the methods used for the synthesis of long DNA fragments, here we constructed a novel shuttle vector named p GF(plasmid Genome Fast) for DNA assembly in vivo. The BAC plasmid p CC1 BAC, which can accommodate large DNA molecules, was chosen as the backbone. The sequence of the yeast artificial chromosome(YAC) regulatory element CEN6-ARS4 was synthesized and inserted into the plasmid to enable it to replicate in yeast. The selection sequence HIS3, obtained by polymerase chain reaction(PCR) from the plasmid p BS313, was inserted for screening. This new synthetic shuttle vector can mediate the transformation-associated recombination(TAR) assembly of large DNA fragments in yeast, and the assembled products can be transformed into Escherichia coli for further amplification. We also conducted in vivo DNA assembly using p GF and yeast homologous recombination and constructed a 31-kb long DNA sequence from the cyanophage PP genome. Our findings show that this novel shuttle vector would be a useful tool for efficient genome-scale DNA reconstruction. | Zheng Hou Zheng Zhou Zonglin Wang Gengfu Xiao | 2016 | Virologica Sinica2016，31，2： | 3 |
| 15 | Structure-activity relationship optimization for lassa virus fusion inhibitors targeting the transmembrane domain of GP2显示文摘Dear Editor,Lassa virus(LASV)belongs to the Mammarenavirus genus,Arenaviridae family.Arenaviruses are classified into two main groups-Old World(OW)and New World(NW)-based on virus genetics,serology,antigenic properties and geographical relationships.The OW LASV and Lujo virus(LUJV),as well as NW Jurn'n virus(JUNV),Machupo virus(MACV),Guanarito virus(GTOV),Sabia virus(SABV)and Chapare virus(CHAPV),are known to cause severe hemorrhagic fever and are listed as biosafety level 4(BSL-4)agents.The arenavirus glycoprotein complex(GPC)contains three subunits-the retained stable-signal peptide(SSP),the receptor-binding subunit GP1,and the membrane fusion subunit GP2(Lenz et al.,2001).Notably,the proximate external membrane region and TM of GP2,together with the ectodomain loop and TMs of SSP,form an SSP-GP2 interface,playing essential roles in regulating membrane fusion,and providing targets for distinct fusion inhibitors(Larson et al.,2008;Lee et al.,2008;York et al.,2008;York and Nunberg,2009;Thomas et al.,2011;Burgeson et al.,2013a;Shankar et al.,2016;Wang et al.,2016;Wang et al.,2018).Among these inhibitors,ST-161 is LASV specific(Burgeson et al.,2013a).In this study,we conducted structure-activity relationship(SAR)optimization of ST-161.As a result,21 derivatives with IC50 values<1 pmol/L are presented in Table S1.Hit compounds 21,29 and 57 exhibiting robust inhibition of the LASV pseudotype virus(LASVpv,VSV backbone enveloped by LASV GPC with single cycle infection)entry with IC50 values lower than 0.2 nmol/L(Figs.1A and S1),as well as hit compound 72 with an ester bond instead of acylhydrazone,were further investigated.To test whether the four hit compounds inhibit LASV entry by blocking the GPC-mediated membrane fusion,the inhibition effects of these compounds against LASV GPC mediated fusion were quantitatively determined by dual-luciferase assay(Thomas et al.,2011;Wang et al.,2018). | Guangshun Zhang Junyuan Cao Yan Cai Yang Liu Yanli Li Peilin Wang Xiaoying Jia Mengmeng Zhang Gengfu Xiao Yu Guo Wei Wang | 2019 | Protein & Cell2019，10，2： | 3 |
| 16 | Blocking peptides against HBV: PreS1 protein selected from a phage display library显示文摘 | Wei Wang Yang Liu Xiangyang Zu Rui Jin Gengfu Xiao | 2011 | Biochemical and Biophysical Research Communications2011，，4： | 2 |
| 17 | Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in mouse model显示文摘Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deaths in children globally per year.Furthermore,nearly all children can be infected with RSV by 2 years of age,and individuals can be repeatedly re-infected with RSV throughout life,which poses great threats to infants,the elderly. | Ruxue Zhang Yumin Zhang Wei Zheng Weijuan Shang Yan Wu Ning Li Jun Xiong Hualiang Jiang Jingshan Shen Gengfu Xiao Yuanchao Xie Leike Zhang | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 2 |
| 18 | Rural-urban and Regional Inequality in Output,Income and Consumption in China under Economic Reforms显示文摘 | YaoShujie ZhangZongyi Feng Gengfu | 2005 | Journal of Economic Studies2005，32，1： | 1 |
| 19 | Reticulon 3 attenuates the clearance of cytosolie prion aggregates via inhibiting au- tophagy显示文摘 | Chert Rui Jin Rui Wu Lu Ye Xiaofei Yang Yi Luo Kan Wang Wenxi Wu Di Ye Xing Huang Liqin Huang Tao Xiao Gengfu | 2011 | Autophagy2011，7，2： | 1 |
| 20 | A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir显示文摘During the ongoing pandemic,providing treatment consisting of effective,low-cost oral antiviral drugs at an early stage of SARSCoV-2 infection has been a priority for controling COVID-19.Although Paxlovid and molnupiravir have received emergency approval from the FDA,some side effect concerns have emerged,and the possible oral agents are stillimited,resulting in optimized drug development becoming an urgent requirement. | Yumin Zhang Yuan Sun Yuanchao Xie Wejuan Shang Zhen Wang Hualiang Jiang Jingshan Shen Gengfu Xiao Leike Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 1 |
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