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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

Gao, Ping, Xueshun Wang, Lin Sun, Xiqiang Cheng, Vasanthanathan Poongavanam, Jacob Kongsted, Mar Álvarez, et al. “Design, synthesis, and biologic evaluation of novel galloyl derivatives as HIV-1 RNase H inhibitors..” Chem Biol Drug Des 93, no. 4 (April 2019): 582–89. https://doi.org/10.1111/cbdd.13455.

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Wu, Haifeng, Guoxu Ma, Qinwen Yang, Yindi Zhu, Li Huang, Yu Tian, Xiaoming Yang, et al. “Discovery and synthesis of novel beesioside I derivatives with potent anti-HIV activity..” Eur J Med Chem 166 (March 15, 2019): 159–66. https://doi.org/10.1016/j.ejmech.2019.01.020.

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Kang, Dongwei, Heng Zhang, Zhao Wang, Tong Zhao, Tiziana Ginex, Francisco Javier Luque, Yang Yang, et al. “Identification of Dihydrofuro[3,4- d]pyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors with Promising Antiviral Activities and Desirable Physicochemical Properties..” J Med Chem 62, no. 3 (February 14, 2019): 1484–1501. https://doi.org/10.1021/acs.jmedchem.8b01656.

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