主要研究内容包括：

1、HIV入侵膜融合机制及抑制剂；

2、艾滋病功能性治愈基因治疗策略；

3、病毒疫苗、中和抗体及抗病毒药物。

在研课题：

1、“十三五”艾滋病和病毒性肝炎等重大传染病防治科技重大专项“基于强效HIV进入抑制剂的暴露前预防策略研究”（2018ZX10301103），首席专家；

2、国家自然科学基金重点项目“HIV感染膜融合的动力学及分子机制研究”（81630061），项目负责人；

3、院校“医学与健康科技创新工程”重大协同创新项目“艾滋病功能性治愈及免疫重建”（2017-I2M-1-014），首席专家；

4、“高效抗艾滋病病毒多肽药物”项目（横向课题），项目负责人；

5、“冠状病毒融合抑制剂多肽药物”项目（横向课题），项目负责人。

近5年代表性论文：

1. Xue J*, Chong H, Zhu Y, Zhang J, Tong L, Lu J, Chen T, Cong Z, Wei Q,He Y*. Efficienttreatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide. Cell. 2022; 185:131-144.

2. Chen Y, Jin H*, Tang X, Li L, Geng X, Zhu Y, Chong H, He Y*. Cell membrane-anchored anti-HIV single-chain antibodies andbifunctional inhibitors targeting the gp41 fusion protein: new strategies forHIV gene therapy. Emerg Microbes Infect. 2022; 11(1):30-49.

3.  Zhu Y, Yu D, Hu Y, Wu T, Chong H, He Y*. SARS-CoV-2 derived fusion inhibitorlipopeptides exhibit highly potent and broad-spectrum activity againstdivergent human coronaviruses. Signal Transduct TargetedTher, 2021; 6:294.

4. Yu D, Zhu Y, Jiao T, Wu T, XiaoX, Qin B, Hu Y, Chong H, Lei X, Ren L, Cui S*, Wang J*, HeY*. Structure-baseddesign and characterization of novel fusion-inhibitory lipopeptides againstSARS-CoV-2 and emerging variants. Emerg Microbes Infect. 2021;10(1):1227-1240.

5. Yu D,Zhu Y, Yan H, Wu T, Chong H, He Y*. Pan-coronavirus fusion inhibitors possess potent inhibitory activityagainst HIV-1, HIV-2, and simian immunodeficiency virus. Emerg Microbes Infect. 2021;10(1):810-821.

6. Jin H, Tang X, Li L, Chen Y, Zhu Y, Chong H, He Y*. Generation of HIV-resistant cells with asingle-domain antibody: implications for HIV-1 gene therapy. Cell Mol Immunol. 2021; 18: 660-674.

7. Zhu Y, Yu D, Han Y, Yan H, Chong H, Ren L, Wang J*, Li T*, He Y*. Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals. Sci Adv. 2020; 6(45):eabc9999.

8. Yu D, Xue J, Wei H, Cong Z, Chen T, ZhuY, Chong H, Wei Q, Qin C, He Y*. Therapeutic efficacy and resistance selection of a lipopeptide fusioninhibitor in simian immunodeficiency virus (SIV)-infected rhesus macaques. J Virol. 2020;94(15): e00384-20.

9. Zhu Y, Yu D, Yan H, ChongH, He Y*. Design of potent membrane fusion inhibitorsagainst SARS-CoV-2, an emerging coronavirus with high fusogenic activity. J Virol. 2020;94(14): e00635-20 (Spotlight).

10. Zhu Y, Ding X, Yu D, Chong H, He Y*. The tryptophan-rich motif of HIV-1 gp41 can Interact with the N-terminal deep pocket site: new insights into the structure and function of gp41 and its inhibitors. J Virol. 2020; 94(1): e01358-19.

11. YuD, Su Y, Ding X, Zhu Y, Qin B,Chong H, Cui S, He Y*. Structuraland Functional Characterization of the Secondary Mutation N126K Selected byVarious HIV-1 Fusion Inhibitors. Viruses. 2020; 12(3): E326.

12. Wei H, Yu D,Geng X, He Y*. Defective HIV-1envelope gene promotes the evolution of the infectious strain through recombination in vitro. BMCInfect Dis. 2020; 20 (1):569

13. Tang X, Jin H,Chen Y, Li L, Zhu Y, Chong H, He Y*. A Membrane-anchored short-peptide fusion inhibitor fully protects target cells from infections of HIV-1, HIV-2,and simian immunodeficiency virus. J Virol. 2019; e01177-19.

14. Zhu Y, Chong H, YuD, Guo Y, ZhouY, He Y*. Design and characterization of cholesterylated peptide HIV-1/2 fusion inhibitors with extremely potent and long-lasting antiviral activity. J Virol. 2019; 93(11): e02312-18.

15. ChongH, Xue J, Zhu Y, Cong Z, Chen T, Wei Q, Qin C*, He Y*. Monotherapy with alow-dose lipopeptide HIV fusion inhibitor maintains long-term viral suppressionin rhesus macaques. PLoS Pathog. 2019;15(2):e1007552. 

16. Zhang X, Ding X, Zhu Y, Chong H, Cui S,He J, Wang X, He Y*. Structural and functional characterization of HIV-1 cell fusion inhibitor T20. AIDS. 2019; 33(1):1-11.

17. Geng X, LiuZ, Yu D, QinB, Zhu Y, CuiS, Chong H, He Y*. Conserved Residue Asn-145 in the C-Terminal HeptadRepeat Region of HIV-1 gp41 is Critical for Viral Fusion and Regulates theAntiviral Activity of Fusion Inhibitors. Viruses. Viruses. 2019; 11(7): E609.

18. Chong H, Zhu Y, Yu D, He Y*. Structural and functional characterization of membrane fusion inhibitors with extremely potent activity against human immunodeficiency virus Type 1 (HIV-1), HIV-2, and simian immunodeficiency virus. J Virol. 2018; 92(20):e01088-18.

19. Yu D, Ding X, Liu Z, Wu X, Zhu Y, Wei H,Chong H, Cui S, He Y*. Molecular mechanism of HIV-1 resistance to sifuvirtide, a clinical trial-approved membrane fusion inhibitor. J Biol Chem. 2018; 293(33):12703-12718.

20. Zhu Y, Zhang X, Ding X, Chong H, Cui S, He J, Wang X, He Y*. Exceptional potency and structural basis of a T1249-derived lipopeptide fusion inhibitor against HIV-1, HIV-2, and simian immunodeficiency virus. J Biol Chem. 2018; 293(14):5323-5334.

21. Chong H, Xue J, Zhu Y, Cong Z, Chen T,Guo Y, Wei Q, Zhou Y, Qin C*, He Y*. Design of novel HIV-1/2 fusion Inhibitors with high therapeutic efficacy in rhesus monkey models. J Virol. 2018; 92(16): e00775-18. 

22. Wu X, Liu Z, Ding X, Yu D, Wei H, Qin B,Zhu Y, Chong H, Cui S*, He Y*. Mechanism of HIV-1 resistance to an electronically constrained α-helical peptide membrane fusion Inhibitor. J Virol. 2018; 92(7):e02044-17.

23. Ding X, ZhangX, Chong H, Zhu Y, Wei H, Wu X, He J, Wang X*, He Y*. Enfuvirtide (T20)-based lipopeptide is a more potent HIV-1 cell fusion inhibitor: implication for viral entry and inhibition. J Virol. 2017; 91(18):e00831-17.

24. ZhangX, Zhu Y, Hu H, Zhang S, Wang P, Chong H, He J, Wang X, He Y*. StructuralInsights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion InhibitorsTargeting the Gp41 Pocket. Front CellInfect Microbiol. 2018; 8:51.

25. ChongH, XueJ, XiongS, CongZ, DingX, ZhuY, LiuZ, ChenT, FengY, HeL, GuoY, WeiQ, ZhouY, QinC*, He Y*. A lipopeptide HIV-1/2 fusion inhibitor with highly potent in vitro, ex vivo and in vivo antiviral activity. J Virol. 2017; 91(11):e00288-17.

26. Xiong S, Borrego P, Ding X, ZhuY, Martins A, Chong H, Taveira N*, He Y*. A helical short-peptide fusion inhibitor with highly potent activity against HIV-1, HIV-2 and simian immunodeficiencyvirus. J Virol. 2017; 91(1):e01839-16.

27. Qiao Y, Man L, Qiu Z, Yang L, SunY, He Y*. Isolation and characterization of a novel neutralizing antibody targeting the CD4-binding site of HIV-1 gp120. Antiviral Res. 2016; 132:252-61.

28. Chong H, Wu X, Su Y, He Y*. Development of potent and long-acting HIV-1 fusion inhibitors. AIDS. 2016; 30(8): 1187-1196.

29. Su Y, Chong H, Xiong S, QiaoY, Qiu Z, He Y*. Genetic pathway of HIV-1 resistance to novel fusion inhibitors targeting the gp41 pocket. J Virol. 2015;89(24):12467-12479.

30. Chong H, Qiu Z, Su Y, He Y*. The N-terminal T-T motif of a third-generation HIV-1 fusion inhibitor is not required for binding affinity and antiviral activity. J Med Chem. 2015; 58(16): 6378-6388.

31. Qiu Z, ChongH, Yao X, Su Y, Cui S*, He Y*. Identification and characterization of a sub-pocket on the N-trimer of HIV-1 gp41: implication for viral entry and drug target. AIDS. 2015; 29(9):1015-1024.

32. Su Y, Chong H,Qiu Z, Xiong S, He Y*. Mechanism of HIV-1 resistance to short peptide fusion inhibitors targeting the gp41 pocket. J Virol. 2015; 89(11):5801-11. 

33. ChongH, Qiu Z, Su Y, Yang L, He Y*.Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket. AIDS. 2015; 29(1):13-21.

                                                                   国家I类抗艾滋病新药“利普韦肽”获批进入临床试验

     2020年6月30日，中国医学科学院病原生物学研究所与合作单位山西康宝生物制品股份有限公司收到国家药品监督管理局颁发的《临床试验通知书》，同意国家1类抗艾滋病新药“利普韦肽”开展临床试验。

    利普韦肽是何玉先教授团队历经10年不懈努力研发的多肽类人免疫缺陷病毒（HIV）膜融合抑制剂，具有独立知识产权。2016年10月18日，我所与山西康宝生物制品股份有限公司签署“技术转让及合作协议书”，双方通过密切合作进行利普韦肽的临床转化研究。研发团队利用近3年的时间，先后完成药物合成工艺、中试生产、制剂制备、药效药代和安全毒理等一系列临床前实验研究，于2019年底向国家药品评审中心提交申报资料，2020年4月9日获得正式受理。

    目前，美国FDA已批准30多种药物用于艾滋病的临床治疗，其中仅有多肽药物恩夫韦肽（又名T20）为HIV膜融合抑制剂。由于T20抗病毒活性相对较低，且容易诱导耐药，极大地限制它的临床应用。利普韦肽是在对HIV融合蛋白结构与功能深入研究的基础上通过理性设计而获得的强效膜融合抑制剂，其在猴和大鼠体内具有良好的药代动力学特征和安全性，成药性较高。与T20相比，利普韦肽对各种亚型HIV的抑制活性提高数千倍之多，而且对T20耐药病毒株也高度有效；在恒河猴SHIV感染模型，利普韦肽单独给药可以迅速将病毒载量降到检测线以下水平，表现出长效的治疗效果。研发团队正在积极部署利普韦肽I期临床试验相关事项，有望在今年获得临床安全性和有效性基本数据。