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Antiviral Drug Discovery Laboratory

Photo of Chin-Ho Chen, PhD

Chin-Ho Chen, PhD

Office: SORF Bldg Room 117 Durham, NC 27710
Phone: 919-684-3819

Scientific Focus

The Laboratory of Antiviral Drug Discovery conducts research for the development of novel therapeutics against HIV-1 and influenza viruses.

  • Novel small molecules against HIV-1 and influenza viruses
  • Identification of biological active principles from natural products
  • Lead optimization of antivirals
  • Molecular mechanisms of antiviral actions

Selected Achievements

 

  1. Discovery of HIV-1 entry inhibitors through studying HIV-1 Env-mediated cell-cell fusion. We study the structure and function of HIV-1 envelope glycoproteins with a goal of identifying inhibitors that can block HIV-1 entry. We are among the pioneers in defining the helix-helix interaction in gp41 that is critical for HIV-1 entry. Eventually, this led to the development of the FDA-approved HIV-1 fusion inhibitor, Fuzeon, which inhibits the helix-helix interaction of gp41. The discovery of the helix-helix interaction in gp41 is the theoretical basis for the development of the HIV-1 fusion inhibitor, Fuzeon. We believe small-molecule HIV-1 entry inhibitors also have potential to become useful additions to current antiretroviral therapy.
  2. Development of anti-HIV bi-functional betulinic acid derivatives. We have synthesized a class of betulinic acid derivatives that targets both HIV entry and maturation.
  3. Development of anti-HIV maturation inhibitor that can overcome bevirimat resistance observed in clinical trials.
  4. We have discovered that a daphnane diterpene, gnidimacrin, can inhibit HIV-1 entry at pM concentration. Gnidimacrin also activates HIV from latently infected cells and leads to the elimination of infected cells. Thus, gnidimacrin may also become a useful agent for purging HIV-1 from latent HIV reservoirs.
  5. Discovery of novel influenza virus inhibitors.

Contact Us

Li Huang: lihuang@duke.edu

Latest Publications

Sun, Songkai, Boshi Huang, Zhuo Li, Zhao Wang, Lin Sun, Ping Gao, Dongwei Kang, et al. “Discovery of potential dual-target prodrugs of HIV-1 reverse transcriptase and nucleocapsid protein 7.” Bioorg Med Chem Lett 30, no. 16 (August 15, 2020): 127287. https://doi.org/10.1016/j.bmcl.2020.127287.

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Li, Jian-Chun, Wei-Feng Dai, Dan Liu, Ming-Yan Jiang, Zhi-Jun Zhang, Xuan-Qin Chen, Chin-Ho Chen, Rong-Tao Li, and Hong-Mei Li. “Bioactive ent-isopimarane diterpenoids from Euphorbia neriifolia.” Phytochemistry 175 (July 2020): 112373. https://doi.org/10.1016/j.phytochem.2020.112373.

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Lu, Yan, Ya-Si Huang, Chin-Ho Chen, Toshiyuki Akiyama, Susan L. Morris-Natschke, Yung-Yi Cheng, Ih-Sheng Chen, Sheng-Zehn Yang, Dao-Feng Chen, and Kuo-Hsiung Lee. “Anti-HIV tigliane diterpenoids from Reutealis trisperma.” Phytochemistry 174 (June 2020): 112360. https://doi.org/10.1016/j.phytochem.2020.112360.

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Sun, Lin, Tianguang Huang, Alexej Dick, Megan E. Meuser, Waleed A. Zalloum, Chin-Ho Chen, Xiao Ding, et al. “Design, synthesis and structure-activity relationships of 4-phenyl-1H-1,2,3-triazole phenylalanine derivatives as novel HIV-1 capsid inhibitors with promising antiviral activities.” Eur J Med Chem 190 (March 15, 2020): 112085. https://doi.org/10.1016/j.ejmech.2020.112085.

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