• Therapeutic Agents Discovery for the Treatment of Autoimmune Diseases  
  At the first stage, we have successfully formed a highly efficient screening and evaluation system for immunosuppressive drug candidate discovery which includes in vitro and in vivo study. Worthy of mention in this system are several animal models of common human auto immune diseases: Type II bovine collagen (CII)-induced arthritis (CIA) in DBA/1 mice served as a model for RA; Myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice served as a model for MS; SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr mice served as a model for SLE.  
  At the second stage, we tested thousands of compounds and components from CTHM to identify active substances in vitro and then studied the therapeutical effects of the promising compounds using animal models in vivo. 5 series of promising candidates for the treatment of autoimmune diseases. Among these, 4 series of candidates are from natural products.
  (1)  (5R)-5-hydroxytriptolide (LLDT-8) is a new derivative of triptolide, which defined as the active component in Tripterygium wilfordii Hook. F. Our studies showed that LLDT-8 possessed low cytotoxicity and relative high immunosuppressive activities when compared with triptolide. LLDT-8, as an anti-arthritic drug candidate, successfully transferred to Shanghai Pharmaceutical (Group) Co.,Ltd, has already completed the Phase I clinical trial. 
  (2)  Antimarlarial agents Artemisinin and its derivatives demonstrated immunosuppressive activity in vitro and in vivo. SM934, a new water soluable derivative of artemisinin, displayed powerful immunosuppressive activities in vivo and in vitro. SM934 showed therapeutic activity in MRL/lpr-lpr mice with SLE. As a novel drug candidate for the treatment of systemic lupus erythematosus (SLE), has already completed the preclinical trial and is through the IND application process.
  (3) Periplocoside E (PSE), a pregnane glycoside had been identified from Periploca sepium Bge, which was used for treating autoimmune disease in ancient China. Our studies confirmed that PSE reduced the incidence and severity of rheumatoid arthritis. These findings suggest the potential therapeutic effect of PSE on RA.
  (4) Besides the candidates from TCM, Dr. Zuo’s group also studied the abnormal activation of AdoHcy hydrolase in the pathology of CIA, EAE and SLE, in order to develop the type III inhibitor of AdoHcy hydrolase. DZ2002 as a new treatment for autoimmune diseases. The results indicated that the therapeutic effects of DZ2002 may be related on the inhibition on both T cells and APC activation and suggested its utility in the treatment of lupus.
• Therapeutic Agents Discovery for the Treatment of Viral infectious Diseases  
  Establishment of platform for screening anti-virus drugs: such as anti-HBV, anti-HCV, anti-Dengue virus and anti-influenza virus platform establishment. Platform including HTS based on targeted molecular identification, cell-based screening on activity, and animal model of disease. 
  Anti-HBV drug study:
  Through the cell-based anti-HBV drug screening and the structure-activity relationship study, we have found several series of small non-nucleotide compounds with simple structure, which showed high efficacy against HBV-DNA replication and with low cytotoxicity in vitro, such as NZ-4 series (chemmedchem,2008), benzimidazole series (EJMC,2007;JMC,2006), QH series, polyphenol series and Chinese herbal extracts.
  (1)  NZ-4 series: showed promising correlation between in vitro DNA replication inhibitory activity and in vivo efficacy in DHBV-infected ducks model, good PK profile and low toxicity. In this series of compounds, NZ-4 was selected as candidate against HBV, successfully transferred to Shanghai Haihe Pharmaceutical (Group) Co.,Ltd, has already completed the Phase I clinical trial.
  (2)  benzimidazole derivatives: IC50 for HBV-DNA replication=0.04-10.5μM.  
  Anti-HCV drug study:
  Con1 cell line with HCV replicon is being used in the group, and now an infectious virus with eGFP can be used to infect Huh7.5.1 cell for anti-HCV drugs screening, and ribavirin show activity on both of the screening systems.
  QH series, IC50 for HCV-DNA replication = 0.4-5.4μM, successfully transferred to Tianjin Hongri Pharmaceutical (Group) Co.,Ltd, is in the preclinical development process.

Editorial boards

1. Associate Editors-in-chief of Acta Pharmacologica Sinica
2. EDITOR of Journal of Cellular and Molecular Medicine, Drug Discoveries & Therapeutics、Virologica Sinica、Chinese Pharmaceutical Journal、Chinese Biological Abstracts.

Professional committees

1. Chairman, Shanghai Pharmacological Society
2. executive director, Chinese Pharmacological Society
3. member of the Standing Committee, Biological safety and protective equipment board, Chinese Preventive Medicine Association
4. committee member, National Pathogenic Microbiology Laboratory Biosafety Committee, China Ministry of Science and Technology
5. committee member, Chinese Association for Laboratory Animal Sciences
6. member of the Standing Committee, Laboratory Bio-safety Committee, China Medicinal Biotech Association
7. committee member, Shanghai Pharmaceutical Association
8. committee member, Shanghai Society for Immunology

(2009.01.01- current)

1. Xu YB, Yang L, Wang GF, Tong XK, Wang YJ, Yu Y, Jing JF, Feng CL, He PL, Lu W, Tang W, Zuo JP*. Benzimidazole Derivative, BM601, a Novel Inhibitor of Hepatitis B Virus and HBsAg Secretion. Antiviral Res. Antiviral Res. 2014 Apr 15;107C:6-15

2. Yang L, Shi LP, Chen HJ, Tong XK, Wang GF, Zhang YM, Wang WL, Feng CL, He PL, Zhu FH, Hao YH, Wang BJ, Yang DL, Tang W, Nan FJ, Zuo JP*. Isothiafludine, a novel non-nucleoside compound, inhibits hepatitis B virus replication through blocking pregenomic RNA encapsidation. Acta Pharmacol Sin. 2014 Mar;35(3):410-8

3. He SJ, Lin ZM, Zhang XH, Wu YW, Bai BX, Yang XQ, He PL, Zhu FH, Tang W*, Zuo JP*. Therapeutic effect of a reversible S-adenosyl-L-homocysteine hydrolase inhibitor in lupus-prone NZB×NZW F1 mice via interfering Toll-like receptor engaged antigen-presenting cell responses. Acta Pharmacol Sin. 2014 Feb;35(2):219-29

4. Li X, Li TT, Zhang XH, Hou LF, Yang XQ, Zhu FH, Tang W*, Zuo JP*. Artemisinin Analogue SM934 Ameliorates Murine Experimental Autoimmune Encephalomyelitis through Enhancing the Expansion and Functions of Regulatory T Cell. PLoS One. 2013 Aug 29;8(8):e74108

5. Kong FY, Chen W, He SJ, Lin ZM, Li X, Zhang XH, Yang XQ, Zhu FH, Tong XK, Zhou Y, Tang W, Duan WH*, Zuo JP*. Mycophenolic Acid Derivative 118 Treated Acute Skin Grafting Diseases through Suppressing the IL-17 Production. Acta Pharmacol Sin. 2013 Jul;34(7):921-9

6. Wan CP, Gao LX, Hou LF, Yang XQ, He PL, Yang YF, Tang W, Yue JM*, Li J*, Zuo JP*. Astragaloside triggers T cell activation through regulating the activity of CD45 protein tyrosine phosphatase. Acta Pharmacol Sin. 2013 Apr;34(4):522-30

7. Shi JJ, Ji FH, He PL, Yang YX, Tang W, Zuo JP, Li YC. Synthesis and hepatitis C antiviral activity of 1-aminobenzyl-1H-indazole-3-carboxamide analogues. ChemMedChem. 2013 May;8(5):722-5

8. Lu Y, Chen B, Song JH, Zhen T, Wang BY, Li X, Liu P, Yang X, Zhang QL, Xi XD, Chen SD, Zuo JP, Chen Z, Chen SJ. Eriocalyxin B ameliorates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2258-63

9. Du YJ, Lin ZM, Zhao YH, Feng XP, Wang CQ, Wang G, Wang CD, Shi W, Zuo JP, Li F, Wang CZ. Stability of the recombinant anti？erbB2 scFv？Fc？interleukin？2 fusion protein and its inhibition of HER2？overexpressing tumor cells. Int J Oncol. 2013 Feb;42(2):507-16

10. Feng E, Shin WJ, Zhu X, Li J, Ye D, Wang J, Zheng M, Zuo JP, No KT, Liu X, Zhu W, Tang W, Seong BL, Jiang H, Liu H. Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors. J Med Chem. 2013 Feb 14;56(3):671-84

11. Zhang B, Wang Y, Yang SP, Zhou Y, Wu WB, Tang W, Zuo JP, Li Y, Yue JM. Ivorenolide A, an unprecedented immunosuppressive macrolide from Khaya ivorensis: structural elucidation and bioinspired total synthesis. J Am Chem Soc. 2012 Dec 26;134(51):20605-8

12. Tang W, Zuo JP*. Immunosuppressant discovery from Tripterygium wilfordii Hook f: the novel triptolide analog (5R)-5-hydroxytriptolide (LLDT-8). Acta Pharmacol Sin. 2012 Sep;33(9):1112-8

13. Ye D, Shin WJ, Li N, Tang W, Feng E, Li J, He PL, Zuo JP, Kim H, Nam KY, Zhu W, Seong BL, Tai No K, Jiang H, Liu H. Synthesis of C-4-modified zanamivir analogs as neuraminidase inhibitors and their anti-AIV activities. Eur J Med Chem. 2012 Aug;54:764-70

14. Hou LF, He SJ, Li X, Wan CP, Yang Y, Zhang XH, He PL, Zhou Y, Zhu FH, Yang YF, LiY, Tang W, Zuo JP*. SM934 Treated Lupus-prone NZB × NZW F1 Mice by Enhancing Macrophage Interleukin-10 Production and Suppressing Pathogenic T Cell Development. PLoS ONE. 2012(7)2:e32424. doi:10.1371/journal.pone. 0032424

15. Deng J, Li N, Liu H, Zuo Z, Liew OW, Xu W, Chen G, Tong X, Tang W, Zhu J, Zuo J, Jiang H, Yang CG*, Li J*, Zhu W*. Discovery of Novel Small Molecule Inhibitors of Dengue Viral NS2B-NS3 Protease Using Virtual Screening and Scaffold Hopping. J Med Chem. 2012 Jul 26;55(14):6278-93

16. Liu MM, Zhou L, He PL, Zhang YN, Zhou JY, Shen Q, Chen XW, Zuo JP*, Li W*, Ye DY*. Discovery of flavonoid derivatives as anti-HCV agents via pharmacophore search combining molecular docking strategy. Eur J Med Chem. 2012 Jun;52:33-43

17. Wu J, Zhou Y, Wang LY, Zuo JP, Zhao WM*. Terpenoids from root bark of Celastrus orbiculatus. Phytochemistry 2012 Mar;75:159-68

18. Chao B, Tong XK, Tang W, Li DW, He PL, Jean-Michel Garcia, Zeng LM, Gao AH, Yang L, Li J, Nan FJ, Michael Jacobs, Ralf Altmeyer, Zuo JP*, Hu YH*. Discovery and optimization of 2,4-diaminoquinazoline derivatives as a new class of potent dengue virus inhibitors. J Med Chem. 2012 Apr 12;55(7):3135-43

19. Zhang M, Yang XY, Tang W, Tom W.L.Groeneveld, He PL, Zhu FH, Li J, Lu W, Anna M. Blom, Zuo JP*, Nan FJ*. Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement. ACS Medicinal Chemistry Letters. 2012, 3, 317-321

20. Feng XJ, Yang XY, Luo Y, Li X, Tang W, Zuo JP*, Lu W*. Synthesis and immunomodulating activity of new analogues of fingolimod. Arch Pharm (Weinheim). 2012 Feb;345(2):93-100

21. Wang LY, Chen ZH, Zhou Y, Tang W, Zuo JP, Zhao WM*. Structural revision of periplocosides and periperoxides, natural immunosuppressive agents from the genus Periploca. Phytochemistry. 2011 Dec;72(17):2230-6

22. Xie H, Lin L, Tong L, Jiang Y, Zheng M, Chen Z, Jiang X, Zhang X, Ren X, Qu W, Yang Y, Wan H, Chen Y, Zuo J, Jiang H, Geng M, Ding J*. AST1306, A Novel Irreversible Inhibitor of the Epidermal Growth Factor Receptor 1 and 2, Exhibits Antitumor Activity Both In Vitro and In Vivo. PLoS One. 2011;6(7):e21487

23. Hou LF, He SJ, Li X, Yang Y, He PL, Zhou Y, Zhu FH, Yang YF, Li Y, Tang W, Zuo JP*. Oral administration of Artemisinin analogue SM934 ameliorated the lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis & Rheumatism. 2011 Aug;63(8):2445-55

24. Qu SJ, Wang GF, Duan WH, Yao SY, Zuo JP*, Tan CH*, Zhu DY. Tryptamine derivatives as novel non-nucleosidic inhibitors against hepatitis B virus. Bioorg Med Chem. 2011 May 15;19(10):3120-7

25. Luo Y, Yao JP, Yang L, Feng CL, Tang W, Wang GF, Zuo JP*, Lu W*. Synthesis and anti-hepatitis B virus activity of a novel class of thiazolylbenzimidazole derivatives. Arch Pharm (Weinheim). 2011 Feb;344(2):78-83

26. Wang HB, Zuo JP, Qin GW*. One new sesquiterpene from Saussurea laniceps. Fitoterapia. 2010 Oct;81(7):937-9

27. Luo Y, Yao JP, Yang L, Feng CL, Tang W, Wang GF, Zuo JP*, Lu W. Design and synthesis of novel benzimidazole derivatives as inhibitors of hepatitis B virus. Bioorg Med Chem. 2010 Jul 15;18(14):5048-55

28. Tong XK, Qiu H, Zhang X, Shi LP, Wang GF, Ji FH, Ding HY, Tang W, Ding K*, Zuo JP*. WSS45, a sulfated alpha-D-glucan, strongly interferes with Dengue 2 virus infection in vitro. Acta Pharmacol Sin. 2010 May;31(5):585-92

29. Ni J, Zhu YN, Zhong XG, Ding Y, Hou LF, Tong XK, Tang W, Ono S, Yang YF*, Zuo JP*. The chemokine receptor antagonist, TAK-779, decreased experimental autoimmune encephalomyelitis by reducing inflammatory cell migration into the central nervous system, without affecting T cell function. Br J Pharmacol. 2009 Dec;158(8):2046-56

30. Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, He PL, Zhang Y, Yang YF, Li Y*, Wei Tang W*, Zuo JP*. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo. Int Immunopharmacol. 2009 Dec;9(13-14):1509-17

31. Wang JX, Hou LF, Yang Y, Tang W, Li Y, Zuo JP*. Inhibition of NO and pro-inflammatory cytokine production by SM905, a novel artemisinin derivative, is associated with suppression of MAPK and NF-κB pathways in RAW 264.7 macrophages. Acta Pharmacol Sin. 2009 Oct;30(10):1428-35

32. Zhang J, Ni J, Chen ZH, Li X, Zhang RJ, Tang W, Zhao WM, Yang YF*, Zuo JP*. Periplocoside A prevents experimental autoimmune encephalomyelitis by suppressing IL-17 production and inhibits differentiation of Th17 cells. Acta Pharmacol Sin. 2009 Aug;30(8):1144-52

33. Wang GF#, Shi LP#, Ren YD#, Liu QF, Liu HF, Zhang RJ, Li Z, Zhu FH, He PL, Tang W, Tao PZ, Li C, Zhao WM, Zuo JP*. Anti-hepatitis B virus activity of chlorogenic acid, quinic acid and caffeic acid in vivo and in vitro. Antiviral Res. 2009 Aug;83(2):186-90

34. Garcia JM, Gao A, He PL, Choi J, Tang W, Bruzzone R, Schwartz O, Naya H, Nan FJ*, Li J*, Altmeyer R, Zuo JP*. High-throughput screening using pseudotyped lentiviral particles: A strategy for the identification of HIV-1 inhibitors in a cell-based assay. Antiviral Res. 2009 Mar;81(3):239-47

35. Zhou R, Tang W, He PL, Yang YF, Li YC, Zuo JP*. (5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells. Int Immunopharmacol. 2009 Jan;9(1):63-9