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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

Rahim, Abdul, Yohei Saito, Shuichi Fukuyoshi, Katsunori Miyake, Masuo Goto, Chin-Ho Chen, Gemini Alam, Kuo-Hsiung Lee, and Kyoko Nakagawa-Goto. “Paliasanines A-E, 3,4-Methylenedioxyquinoline Alkaloids Fused with a Phenyl-14-oxabicyclo[3.2.1]octane Unit from Melochia umbellata var. deglabrata.” J Nat Prod 83, no. 10 (October 23, 2020): 2931–39. https://doi.org/10.1021/acs.jnatprod.0c00454.

Full Text

Otsuki, Kouharu, Wei Li, Kasumi Miura, Yoshihisa Asada, Li Huang, Chin-Ho Chen, Kuo-Hsiung Lee, and Kazuo Koike. “Isolation, Structural Elucidation, and Anti-HIV Activity of Daphnane Diterpenoids from Daphne odora.” J Nat Prod, September 30, 2020. https://doi.org/10.1021/acs.jnatprod.0c00540.

Full Text

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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