許葉春

1995-09--華東師範大學化學系 學士

1999-09--華東師範大學化學系 碩士

2001-09--中國科學院上海藥物研究所 博士

2005-07--以色列魏茨曼科學研究所 博士後 ^[6] 

2004.7-2005.6中國科學院上海藥物研究所（助理研究員）

2005.7-2009.9以色列魏茲曼科學研究所（博士後）

2009.10-至今中國科學院上海藥物研究所（研究員，課題組長） ^[2] 

1、基於結構的先導化合物的從頭設計與優化

2、靶標蛋白與配體的識別作用機制研究 ^[2] 

許葉春研究員及其課題組主要開展基於靶標結構的藥物設計研究，建立了以精準表徵化合物與靶標結合為特色的多學科交叉、多技術整合的先導化合物從頭設計與高效優化研究策略與技術體系，針對感染與炎症密切相關的重要蛋白質，快速發現活性化合物，解析多個關鍵化合物與靶標結合的高分辨率複合物結構，並精確測定化合物與靶標的親和力，從而精準表徵化合物與靶標結合的位點、相互作用模式、構象變化、水分子的作用及熱力學特徵等，同時應用計算機輔助藥物設計方法，高效獲得了多個全新先導化合物及臨牀前、臨牀候選新藥。已發表研究論文及綜述100多篇，其中一作和通訊作者論文61篇，代表性論文包括Science 2篇、Nature 1篇、Nat. Commun. 1篇、Proc. Natl. Acad. Sci. 1篇、J. Am. Chem. Soc. 2篇和J. Med. Chem. 11篇；在PDB中發表晶體結構100多個；申請專利26項；參與研發的PDE5抑制劑進入治療肺動脈高壓的II期臨牀研究，參與研發的抗COVID-19 SARS-CoV-2 3CL蛋白酶抑制劑已申報臨牀批件並實現成果轉化，主持研發的抗銀屑病PDE4抑制劑進入系統的臨牀前評價研究，即將申報臨牀批件；主持了國家自然科學基金優秀青年科學基金項目及國際合作項目、國家重點研發計劃項目課題、中國科學院戰略性先導科技專項子課題、上海市“浦江人才”和上海市政府間國際科技合作項目等科研項目。 ^[2] 

2009中科院-諾和諾德長城教授獎

2005-2008魏茲曼科學研究所院長獎學金

2006全國百篇優秀博士論文

2005中國科學院優秀博士學位論文；中國藥學會-“施維雅”青年藥物化學獎

2020年11月7日，獲得第七屆樹蘭醫學獎樹蘭醫學青年獎。 ^[1] 

2022年7月，榮獲第十七屆“中國青年女科學家獎”。 ^[3-4] 

2019.1-2022.121、國家自然科學基金面上項目（主持）

2019.4-2022.32、上海市2019年度“科技創新行動計劃”生物醫藥領域科技支撐項目（主持）

2019.1-2020.123、中國科學院戰略性先導科技專項子課題（主持）

2018.4-2021.34、上海市國際科技合作基金項目（主持）

2017.7-2020.125、國家重點研發計劃基於E級高性能計算生物醫藥應用軟件系統研製及應用項目課題四（主持） ^[2] 

1.HX Su#, S Yao#, WF Zhao#, MJ Li#, J Liu#, WJ Shang#, H Xie, CQ Ke, HC Hu, MN Gao, KQ Yu, H Liu, JS Shen, W Tang, LK Zhang, GF Xiao, L Ni, DW Wang, JP Zuo, HL Jiang, F Bai*, Y Wu*, Y Ye*, YC Xu*. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol. Sin. 2020, 41(9):1167-1177.

2.WF Zhao#, MY Xiong#, XJ Yuan, MJ Li, HB Sun*, YC Xu*. In silico screening-based discovery of novel inhibitors of human cyclic GMP-AMP synthase: a cross-validation study of molecular docking and experimental testing. J. Chem. Inf. Model. 2020, 60(6), 3265-3276.

3.FB Huang#, HC Hu#, K Wang, CY Peng, WW Xu, Y Zhang, J Gao, YS Liu, H Zhou, RM Huang, MJ Li, JH Shen*, YC Xu*. Identification of highly selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors by a covalent-fragment-based approach. J. Med. Chem. 2020, 63(13),7052-7065.

4.WC Yin#, CY Mao#, XD Luan#, DD Shen#, QY Shen#, HX Su#, XX Wang, FL Zhou, WF Zhao, MQ Gao, SH Chang, YC Xie, GH Tian, HW Jiang, SC Tao, JS Shen, Y Jiang, HL Jiang, YC Xu*, SY Zhang*, Y Zhang*, HE Xu*. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 2020, 368, 1499–1504.

5.WH Dai#, B Zhang#, XM Jiang#, HX Su#, J Li, Y Zhao, X Xie, ZM Jin, JJ Peng, FJ Liu, CP Li, Y Li, F Bai, HF Wang, X Cheng, XB Cen, SL Hu, XN Yang, J Wang, X Liu, GF Xiao, HL Jiang, ZH Rao, LK Zhang*, YC Xu*, HT Yang*, H Liu*. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science, 2020, 368, 1331–1335.

6.ZM Jin#, XY Du#, YC Xu#, YQ Deng#, MQ Liu#, Y Zhao, B Zhang, XF Li, LK Zhang, C Peng, YK Duan, J Yu, L Wang, KL Yang, FJ Liu, RD Jiang, XL Yang, T You, XC Liu, XN Yang, F Bai, H Liu, X Liu, LW Guddat, WQ Xu, GF Xiao, CF Qin, ZL Shi, HL Jiang*, ZH Rao*, HT Yang*. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 2020, 582(7811), 289-293.

7.HX Su#, Y Zou#, GF Chen#, HX Dou#, H Xie, XJ Yuan, XL Zhang, NX Zhang, MJ Li, YC Xu*. Exploration of fragment binding poses leading to efficient discovery of highly potent and orally effective inhibitors of FABP4 for anti-inflammation. J. Med. Chem. 2020, 63(8), 4090-4106.

8.T Chen#, MY Xiong#, X Zong, YJ Ge, H Zhang, M Wang, GW Han, CY Yi, LM Ma, RD Ye, YC Xu*, Q Zhao,* BL Wu*. Structural basis of ligand binding modes at the human formyl peptide receptor 2. Nat. Commun. 2020, 11(1), 1208.

9.XL Zhang#, GY Dong#, H Li#, WY Chen, J Li, CL Feng, ZN Gu, FH Zhu, R Zhang, MJ Li, W Tang*, H Liu*, YC Xu*. Structure-aided identification and optimization of tetrahydro-isoquinolines as novel PDE4 inhibitors leading to discovery of an effective antipsoriasis agent. J. Med. Chem. 2019, 62(11), 5579-5593.

10.Z Wang,# XR Jiang,# XL Zhang,# GH Tian, RL Yang, JZ Wu, XL Zou, Z Liu, XJ Yang, CH Wu, J Shi, JF Li, J Suo, Y Wang, RX Zhang, ZJ Xu, XD Gong, Y He, WL Zhu, HL Jiang,* YC Xu,* JS Shen*. Pharmacokinetic-driven optimization of 4(3H)-pyrimidinones as phosphodiesterase type 5 inhibitors leading to TPN171, a clinical candidate for the treatment of pulmonary arterial hypertension. J. Med. Chem. 2019, 62(10), 4979-4990.

11.HX Su, YC Xu*. Application of ITC-based characterization of thermodynamic and kinetic association of ligands with proteins in drug design. Front. Pharmacol. 2018, 9, 1133.

12.XJ Yuan, S Raniolo, V Limongelli, YC Xu*. The molecular mechanism underlying ligand binding to the membrane-embedded site of a G-protein-coupled receptor. J. Chem. Theory Comput. 2018, 14(5), 2761-2770.

13.QF Liu#, FB Huang#, XJ Yuan#, K Wang, Y Zou, JH Shen*, YC Xu*. Structure-guided discovery of novel, potent and orally bioavailable inhibitors of lipoprotein-associated phospholipase A2. J. Med. Chem. 2017, 60 (24), 10231-10244.

14.YC Xu*, SM Cheng, JL Sussman, IS, HL Jiang. Computational studies on acetylcholinesterases. Molecules 2017, 22, 1324.

15.QF Liu#, XD Chen#, WY Chen, XJ Yuan, HX Su, JH Shen, YC Xu*. Structural and thermodynamic characterization of protein?ligand interactions formed between lipoprotein-associated phospholipase A2 and inhibitors. J. Med. Chem. 2016, 59 (10), 5115-5120.

16.WL Song, H Bajaj, C Nasrallah, HL Jiang, M Winterhalter, JP Colletier*, YC Xu*. Understanding voltage gating of providencia stuartii porins at atomic level. PLoS Comput. Biol. 2015, 11(5), e1004255.

17.J Ren#, Y He#, WY Chen, TT Chen, G Wang, Z Wang, ZJ Xu, XM Luo, WL Zhu, HL Jiang, JS Shen*, YC Xu*. Thermodynamic and structural characterization of halogen bonding in protein-ligand interactions: a case study of PDE5 and its inhibitors. J. Med. Chem. 2014, 57(8), 3588-3593.

18.N Ye#, CH Chen#, TT Chen#, ZL Song, JX He, XJ Huan, SS Song, QF Liu, Y Chen, J Ding, YC Xu,* ZH Miao,* A Zhang.* Design, synthesis and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors. J. Med. Chem. 2013, 56(7), 2885-2903.

19.G Wang#, Z Liu#, TT Chen#, Z Wang, HY Yang, MY Zheng, J Ren, GH Tian, XJ Yang, L Li, JF Li, J Suo, RX Zhang, XR Jiang, NK Terrett, JS Shen,* YC Xu,* HL Jiang.* Design, synthesis, and pharmacological evaluation of monocyclic pyrimidinones as novel inhibitors of PDE5. J. Med. Chem. 2012, 55(23), 10540-10550.

20.YX Liu#, W Zhang#, L Li#, LA Salvador, TT Chen, WY Chen, KM Felsenstein, TB Ladd, AR Price, TE Golde, JH He, YC Xu,* YX Li,* H Luesch.* Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases. J. Med. Chem. 2012, 55(23), 10749-10765.

21.YC Xu*#, MJ Li#, H Greenblatt, WY Chen, A Paz, O Dym, Y Peleg, TT Chen, X Shen, JH He, HL Jiang, IS, JL Sussman*. Flexibility of the flap in the active site of BACE1 as revealed by crystal structures and MD simulations. Acta Crystallogr. D (Biol. Crystallogr.) 2012, D68, 13-25.

22.ZJ Xu#, Z Liu#, T Chen#, TT Chen, Z Wang, GH Tian, J Shi, XL Wang, YX Lu, XH Yan, G Wang, HL Jiang, KX Chen, SD Wang, YC Xu*, JS Shen*, WL Zhu*. Utilization of halogen bond in lead optimization: a case study of rational design of potent phosphodiesterase type 5 (PDE5) inhibitors. J. Med. Chem. 2011, 54(15), 5607-5611.

23.YC Xu*, JP Colletier, M Weik, GR Qin, HL Jiang, I Silman, JL Sussman*. Long route or shortcut? a molecular dynamics study of traffic of thiocholine within the active-site gorge of acetylcholinesterase. Biophys. J. 2010, 99(12), 4003-4011.

24.YC Xu#, JP Colletier#, M Weik, HL Jiang, J Moult, I Silman, JL Sussman*. Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray vs MD. Biophys. J. 2008, 95(5), 2500-2511.

25.YC Xu#, JP Colletier#, HL Jiang, I Silman, JL Sussman, M Weik*. Induced-fit of preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design. Prot. Sci. 2008, 17(4), 601-605.

26.YC Xu#, JH Shen#, XM Luo, WL Zhu, KX Chen, JP Ma*, HL Jiang*. Conformational transition of amyloid ？-peptide. Proc. Natl. Acad. Sci. USA 2005, 102(15), 5403-5407.

27.YC Xu, FJ Barrantes, XM Luo, KX Chen, JH Shen*, HL Jiang*. Conformational dynamics of the nicotinic acetylcholine receptor channel: a 35-ns molecular dynamics simulation study. J. Am. Chem. Soc. 2005, 127(4), 1291-1299.

28.YC Xu, JH Shen*, WL Zhu*, XM Luo, KX Chen, HL Jiang*. Influence of water molecule on cation- interaction: ab initio second order Moller-Plesset perturbation theory (MP2) calculations. J. Phys. Chem. B. 2005, 109(12), 5945-5949.

29.YC Xu, JH Shen*, XM Luo, I Silman, JL Sussman*, KX Chen, HL Jiang*. How does Huperzine A enter and leave the binding gorge of acetylcholinesterase? steered molecular dynamics simulation. J. Am. Chem. Soc. 2003, 125(37), 11340-11349. ^[2]