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| 1 | 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 |
| 2 | Azomethine-H as a Highly Selective Fluorescent Probe for Fe^3+ Detection in 100% Aqueous Solution and Its Application in Living Cell Imaging显示文摘 | YU Fang QIN Liyuan SHANG Zhuobin DONG Zhenming WANG Yu JIN Weijun | 2015 | Chemical Research in Chinese Universities2015，31，6： | 2 |
| 3 | OsMADS32 interacts with PI-like proteins and regulates rice flower development显示文摘OsMADS32 is a monocot specific MIKC^c type MADS-box gene that plays an important role in regulating rice floral meristem and organs identity, a crucial process for reproductive success and rice yield. However, its underlying mechanism of action remains to be clari fied. Here, we characterized a hypomorphic mutant allele of OsMADS32/CFO1, cfo1-3 and identi fied its function in controlling rice flower development by bioinformatics and protein-protein interaction analysis. The cfo1-3 mutant produces defective flowers,including loss of lodicule identity, formation of ectopic lodicule or hull-like organs and decreased stamen number,mimicking phenotypes related to the mutation of B class genes. Molecular characterization indicated that mis-splicing of OsMADS32 transcripts in the cfo1-3 mutant resulted in an extra eight amino acids in the K-domain of OsMADS32 protein.By yeast two hybrid and bimolecular fluorescence complementation assays, we revealed that the insertion of eight amino acids or deletion of the internal region in the K1 subdomain of Os MADS32 affects the interaction between OsMADS32 with PISTILLATA(PI)-like proteins OsMADS2 and OsMADS4. This work provides new insight into the mechanism by which Os MADS32 regulates rice lodicule and stamen identity, by interaction with two PI-like proteins via its K domain. | Huanhuan Wang Liang Zhang Qiang Cai Yun Hu Zhenming Jin Xiangxiang Zhao Wei Fan Qianming Huang Zhijing Luo Mingjiao Chen Dabing Zhang Zheng Yuan | 2015 | Journal of Integrative Plant Biology2015，57，5： | 2 |
| 4 | The effect of smoking on the risk of gallbladder cancer: a meta-analysis of observational studies显示文摘 | Ding Wenbin Chen Zhuo Ming Zhibing Zhou Chen Yuan Ruifan Jin Jie Qian Cheng Ge Zhenming | 2013 | European Journal of Gastroenterology & Hepatology2013，，3： | 1 |
| 5 | Melt topology in partially molten peridotite during ductile deformation 显示文摘 | Jin Zhenming Green W H Zhou Yi | 1994 | Nature1994，372，： | 1 |
| 6 | Unfolding and Conformational Variations of Thrombin‐Binding DNA Aptamers: Synthesis, Circular Dichroism and Molecular Dynamics Simulations显示文摘 | Lidan Sun Hongwei Jin Xiaoyang Zhao Zhenming Liu Yifu Guan Zhenjun Yang Liangren Zhang Lihe Zhang | 2014 | ChemMedChem2014，，5： | 1 |
| 7 | New perspectives on the genetic structure of dotted gizzard shad(Konosirus punctatus)based on RAD-seq显示文摘To maintain,develop and rationally utilize marine organisms,understanding their genetic structure and habitat adaptation pattern is necessary.Konosirus punctatus,which is a commercial fish species inhabiting the Indo-west Pacific Ocean,has shown an obvious annual global capture and aquaculture production decline due to climate changes and human activities.In the present study,restriction-site associated DNA sequencing(RAD-seq)was used to describe its genome-wide single nucleotide polymorphisms panel(SNPs).Among 146 individuals collected at nine locations scattered in China,Korea and Japan,a set of 632,090 SNPs were identified.Population genetic analysis showed that K.punctatus individuals were divided into two significant genetic clusters.Meanwhile,potential genetic differentiation between northern and southern population of K.punctatus was found.Treemix results indicated that gene flow existed among sampling locations of K.punctatus,especially from southern Japan to others.Moreover,candidate genes associated with habitat adaptations of K.punctatus were identified,which are involved in diverse physiological processes of K.punctatus including growth and development(e.g.,KIDINS220,PAN3),substance metabolism(e.g.,PGM5)and immune response(e.g.,VAV3,CCT7,HSPA12B).Our findings may aid in understanding the possible mechanisms for the population genetic structure and local adaptation of K.punctatus,which is beneficial to establish the management and conservation units of K.punctatus,guiding the rational use of resources,with reference significance for a profound understanding of the adaptative mechanisms of other marine organisms to the environment. | Ying Peng Yifan Liu Jiasheng Li Kun Zhang Xun Jin Sixu Zheng Yunpeng Wang Zhenming Lu Liqin Liu Li Gong Bingjian Liu | 2024 | Marine Life Science & Technology2024，6，1： | 0 |
| 8 | High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors显示文摘The global COVID-19 coronavirus pandemic has infected over 109 million people,leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment.Here,we screened about 1.8 million small molecules against the main protease(M^(pro))and papain like protease(PL^(pro)),two major proteases in severe acute respiratory syndrome-coronavirus 2 genome,and identified 1851M^(pro)inhibitors and 205 PL^(pro)inhibitors with low nmol/l activity of the best hits.Among these inhibitors,eight small molecules showed dual inhibition effects on both M^(pro)and PL^(pro),exhibiting potential as better candidates for COVID-19 treatment.The best inhibitors of each protease were tested in antiviral assay,with over 40%of M^(pro)inhibitors and over 20%of PL^(pro)inhibitors showing high potency in viral inhibition with low cytotoxicity.The X-ray crystal structure of SARS-CoV-2 M^(pro)in complex with its potent inhibitor 4a was determined at 1.8Åresolution.Together with docking assays,our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development. | Yi Zang Mingbo Su Qingxing Wang Xi Cheng Wenru Zhang Yao Zhao Tong Chen Yingyan Jiang Qiang Shen Juan Du Qiuxiang Tan Peipei Wang Lixin Gao Zhenming Jin Mengmeng Zhang Cong Li Ya Zhu Bo Feng Bixi Tang Han Xie Ming-Wei Wang Mingyue Zheng Xiaoyan Pan Haitao Yang Yechun Xu Beili Wu Leike Zhang Zihe Rao Xiuna Yang Hualiang Jiang Gengfu Xiao Qiang Zhao Jia Li | 2023 | Protein & Cell2023，14，1： | 0 |
| 9 | Carbazole and tetrahydro-carboline derivatives as dopamine D_(3) receptor antagonists with the multiple antipsychotic-like properties显示文摘Dopamine D_(3) receptor(D_(3)R)is implicated in multiple psychotic symptoms.Increasing the D_(3)R selectivity over dopamine D_2 receptor(D_2R)would facilitate the antipsychotic treatments.Herein,novel carbazole and tetrahydro-carboline derivatives were reported as D_(3)R selective ligands.Through a structure-based virtual screen,ZLG-25(D_(3)R K_i=685 nmol/L;D_2R K_i>10,000 nmol/L)was identified as a novel D_(3)R selective bitopic ligand with a carbazole scaffold.Scaffolds hopping led to the discovery of novel D_(3)R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core.Further functional studies showed that most derivatives acted as h D_(3)R-selective antagonists.Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity.Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction.Furthermore,36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests,and alleviated the MK-801-induced disruption of novel object recognition in mice.Additionally,preliminary studies confirmed the favorable PK/PD profiles,no weight gain and limited serum prolactin levels in mice.These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties. | Zhongtang Li Fan Fang Yiyan Li Xuehui Lv Ruqiu Zheng Peili Jiao Yuxi Wang Guiwang Zhu Zefang Jin Xiangqing Xu Yinli Qiu Guisen Zhang Zhongjun Li Zhenming Liu Liangren Zhang | 2023 | Acta Pharmaceutica Sinica B2023，13，11： | 0 |
| 10 | Interrogating the impact of aggregation-induced emission nanoparticles on in vitro protein stability,ex vivo protein homeostasis,and in vivo biocompatibility显示文摘Aggregation-induced emission(AIE)materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties.A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility.While previous studies focus on cellular viability and toxicity,the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored.Herein,this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis(proteostasis).To this end,four scaffolds of AIE molecules were prepared,further functionalized into eight nanoparticles with two amphiphilic shells respectively,and characterized for their physicochemical properties.Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate,echoed by cell viability and fractionation experiments.Intriguingly,poor polydispersity index(PDI)of functionalized nanoparticles exaggerates their retention and aggregation in the cell.Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network.Finally,vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo,including materials’size,PDI,and treatment frequencies.Overall,amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis. | Wang Wan Qun Zhao Biao Jing Congcong Peng Mengdie Wang Yanan Huang Wenhan Jin Bowen Zhong Zhenduo Zhang Xuepeng Dong Zhenming Gao Lihua Zhang Yu Liu | 2022 | Aggregate2022，3，6： | 0 |
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