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| 1 | 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 |
| 2 | Identification and characterization of loop7 motif and its role in regulating biological function of human APOBEC3G through molecular modeling and biological assay显示文摘Human APOBEC3G(h A3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor(Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the h A3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the h A3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation.Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, h A3G–Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3 G degradation by targeting the putative site around loop7. | Congjie Zhai Ling Ma Zhixin Zhang Jiwei Ding Jing Wang Yongxin Zhang Xiaoyu Li Fei Guo Liyan Yu Jinming Zhou Shan Cen | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 1 |
| 3 | The CREB Regulated Transcription Coactivator 2 Suppresses HIV-1 Transcription by Preventing RNA PolⅡfrom Binding to HIV-1 LTR显示文摘The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increase the infection of several viruses.While human immunodeficiency virus type 1(HIV-1)long terminal repeat(LTR)promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription,it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection.Here,we reported that CRTC2 expression was induced by HIV-1 infection,but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression.Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA PolⅡoccupancy at the LTR independent of its association with CREB.Importantly,CRTC2 inhibits the activation of latent HIV-1.Together,these data suggest that in response to HIV-1 infection,cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency. | Ling Ma Shumin Chen Zhen Wang Saisai Guo Jianyuan Zhao Dongrong Yi Quanjie Li Zhenlong Liu Fei Guo Xiaoyu Li Pingping Jia Jiwei Ding Chen Liang Shan Cen | 2021 | Virologica Sinica2021，36，4： | 1 |
| 4 | Molecular modeling of human APOBEC3G to predict the binding modes of the inhibitor compounds IMB26 and IMB35显示文摘APOBEC3G(A3G)is a host cytidine deaminase that incorporates into HIV-1 virions and efficiently inhibits viral replication.The virally encoded protein Vif binds to A3G and induces its degradation,thereby counteracting the antiviral activity of A3G.Vif-mediated A3G degradation clearly represents a potential target for anti-HIV drug development.Currently,there is an urgent need for understanding the three dimensional structure of full-length A3G.In this work,we use a homology modeling approach to propose a structure for A3G based on the crystal structure of APOBEC2(APO2)and the catalytic domain structure of A3G.Two compounds,IMB26 and IMB35,which have been shown to bind to A3G and block degradation by Vif,were docked into the A3G model and the binding modes were generated for further analysis.The results may be used to design or optimize molecules targeting Vif–A3G interaction,and lead to the development of novel anti-HIV drugs. | Zhixin Zhang Congjie Zhai Zeyun Mi Jiwei Ding Yongxin Zhang Xing Shi Xiaoyu Li Liyan Yu Zhuorong Li Jiandong Jiang Jinming Zhou Shan Cen | 2013 | Acta Pharmaceutica Sinica B2013，3，4： | 0 |
| 5 | On hydraulic falls of two-layer flow显示文摘Onhydraulicfallsoftwo-layerflow￥XuZhaoting;LouShunli;TianJiweiandSamuelShanpnShen(InstituteofPhysicalDeeanopaphyandPhysicaloc... | Xu Zhaoting Lou Shunli Tian Jiwei and Samuel Shan pn Shen(Institute of Physical Deeanopaphy and Physical oceanography Laboratory, Ocean University Of Qngdao, Qngdao266003, China Department of Mathematics and Applied Mathematics institute, University of A | 1996 | Acta Oceanologica Sinica1996，15，2： | 0 |
| 6 | On hydraulic falls of single-layer flow显示文摘Onhydraulicfallsofsingle-layerflow￥XuZhaoting;TianJiwei;LouShunliandSamuelShanpnShen(ReceivedMarch21,1995;acceptedJuly10,1995... | Xu Zhaoting Tian Jiwei Lou Shunli andSamuel Shan pn Shen | 1996 | Acta Oceanologica Sinica1996，15，1： | 0 |
| 7 | Mechanism and morphology evolution of the O phase transformation in Ti-22Al-25Nb alloy显示文摘The phase transformation and microstructure in Ti-22Al-25Nb alloy are extremely complex.In this work,the morphology evolution of the O phase during the heating and cooling process was investigated by electron backscatter diffraction(EBSD)and first-principles calculations.The results show that the O→α_(2)phase transformation process during the heating process is as follows:spheroidization of the O phase occurs first,then theα_(2)phase nucleates in the spheroidized O phase,grows and replaces the O phase,completing the O→α_(2)phase transformation.In the meanwhile,the diffusion of Nb from Nb-poor O to Nb-rich B2 phases is a back-diffusion process.According to first-principles calculations,the driving force of the O→α_(2)phase transformation is the difference in the free energies of formation for the two phases(0.09 eV/atom).When the Nb content is greater than 15.625%,the lattice distortion of theα_(2)phase sharply increases,and the distortion energy drives the back-diffusion of Nb.During the cooling process,theα_(2)→O phase transformation is difficult and slow due to the difficult diffusion of Nb from the B2 toα_(2)phases.When holding for 60 min at 960℃,the coarseα_(2)phase gradually transforms to the O phase from the margin to the inside,forming a dispersed mixed structure of the O andα_(2)phases.During the B2→O transformation,the nucleation of the O phase induces a high stress region,in the range of approximately 200 nm. | Zong Yingying Wang Jiwei Shao Bin Tang Wei Shan Debin | 2021 | Journal of Materials Science & Technology2021，，30： | 0 |
| 8 | SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis显示文摘The coronavirus disease 2019(COVID-19)pandemic has devastated global health.Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks.Here,we have identified host proteins that associate with nonstructural protein 12(nsp12),the RNA-dependent RNA polymerase(RdRp)of SARS-CoV-2 using a mass spectrometry(MS)-based proteomic approach.Among the candidate factors,CDK2(Cyclin-dependent kinase 2),a member of cyclin-dependent kinases,interacts with nsp12 and causes its phosphorylation at T20,thus facilitating the assembly of the RdRp complex consisting of nsp12,nsp7 and nsp8 and promoting efficient synthesis of viral RNA.The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection.Taken together,we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex,thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors. | Saisai Guo Xiaobo Lei Yan Chang Jianyuan Zhao Jing Wang Xiaojing Dong Qian Liu Zixiong Zhang Lidan Wang Dongrong Yi Ling Ma Quanjie Li Yongxin Zhang Jiwei Ding Chen Liang Xiaoyu Li Fei Guo Jianwei Wang Shan Cen | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 0 |
| 9 | Correction to:Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘CORRECTION TO:PROTEIN CELL 2020,11(10):723–739 http://gffzzd3cc09b8251d45dfouwqwwp6cvpv66uuf.ffgz.tsg.suse.edu.cn/10.1007/S13238-020-00768-W In the original publication the author’s name‘Dimitri Lavillete’is published incorrectly.The correct author name should be spelt as‘Dimitri Lavillette’is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http://gffzzeb6f7f563f66445dhuwqwwp6cvpv66uuf.ffgz.tsg.suse.edu.cn/licenses/by/4.0/. | 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 Lavillette Zhenjiang Zhao Rui Wang Lili Zhu Gengfu Xiao Ke Lan Honglin Li Ke Xu | 2022 | Protein & Cell2022，13，10： | 0 |
| 10 | Correction to: Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2显示文摘Figure 1.Discovery of novel and potent DHODHi and their anti-influenza A virus activities.(A)The discovery and design of S312 and S416.The detailed descriptions of the discovery workflow are in Method.Binding analysis of S312(B)and S416(C).Thermodynamic analysis of the binding of S312 and S416 to DHODH was carried out at 25 C on a MicroCal iTC200 instrument.Kinetic analysis of the binding of S312 and S416 to DHODH was performed with a Biacore T200 instrument. | 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 | 2021 | Protein & Cell2021，12，1： | 0 |
| 11 | High depolarization temperature and superior piezoelectric performance with complex structural evolution in BiFeO_(3)-PbTiO_(3)-(Sr0.7Bi0.2,0.1)TiO_(3) systems显示文摘Bismuth ferriteebased ferroelectric ceramics are considered strong competitors in highetemperature piezoelectric applications that benefits from their high depolarization temperature(Td),but problems of large conductivity and low piezoelectric coefficient(d33)should be tackled.BiFeO_(3)ePbTiO_(3)ex(Sr0.7Bi0.2,0.1)TiO_(3)(BFePTexSBT)ternary system are designed in this work that successfully resolves this tough paradox.Rietveld refinements show that this system exhibits multiphase coexistence with complex structural transition among rhombohedral,tetragonal and pseudocubic phase.Interestingly,a high Td~320℃ and d33~236℃/N are synergistically optimized in x=0.20 composition near pseudoephase boundary,which are indicated by multiescale techniques(phase structure,dielectric analysis etc.).What'smore,dual electrostrain peaks appear at separate phase boundaries for x=0.20 and 0.66 compositions with distinct piezo/ferroelectric properties.Rayleigh law and piezoelectric force microscopy analysis clarify that the optimal electrostrain performance for both critical compositions are dominated by intrinsic(x=0.20)and extrinsic(x=0.66)contributions,respectively.This work not only provides a new BFePTexSBT system with a high Td and superior d33 that are promising candidates in highetemperature actuator and sensor applications,but also presents a possibility of multiphaseecoexistence established exotic macroscopic performances. | Hongwei Shi Feng Li Xinliang Yang Mingsheng Long Lei Shan Chunchang Wang Jiwei Zhai | 2022 | Journal of Materiomics2022，8，6： | 0 |
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