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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

Yan, S-L, Li, Y-H, Chen, X-Q, Liu, D, Chen, C-H, and Li, R-T. "Diterpenes from the stem bark of Euphorbia neriifolia and their in vitro anti-HIV activity." Phytochemistry 145 (January 2018): 40-47.

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Dong, M, Quan, L-Q, Dai, W-F, Yan, S-L, Chen, C-H, Chen, X-Q, and Li, R-T. "Anti-inflammatory and Anti-HIV Compounds from Swertia bimaculata." Planta medica 83, no. 17 (November 2017): 1368-1373.

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Chen, C-H, and Poss, KD. "Regeneration Genetics." Annual review of genetics 51 (November 2017): 63-82.

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Dang, Z, Xie, H, Zhu, L, Zhang, Q, Li, Z, Huang, L, and Chen, C-H. "Structure Optimization of Aloperine Derivatives as HIV-1 Entry Inhibitors." ACS medicinal chemistry letters 8, no. 11 (November 2017): 1199-1203.

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