Trilobatin as an HIV-1 entry inhibitor targeting the HIV-1 Gp41 envelope

  • FEBS Lett. 2018 Jul;592(13):2361-2377. doi: 10.1002/1873-3468.13113.
Shuwen Yin  1 ,  Xuanxuan Zhang  1 ,  Fangyuan Lai  1 ,  Taizhen Liang  1 ,  Jiayong Wen  1 ,  Wanying Lin  1 ,  Jiayin Qiu  2 ,  Shuwen Liu  1 ,  Lin Li  1
Affiliations
  • 1. Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
  • 2. School of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.
PMID: 29802645 DOI: 10.1002/1873-3468.13113
Abstract

HIV-1 transmembrane protein gp41 plays a crucial role by forming a stable six-helix bundle during HIV entry. Due to highly conserved sequence of gp41, the development of an effective and safe small-molecule compound targeting gp41 is a good choice. Currently, natural polyanionic ingredients with anti-HIV activities have aroused concern. Here, we first discovered that a glycosylated dihydrochalcone, trilobatin, exhibited broad anti-HIV-1 activity and low cytotoxicity in vitro. Site-directed mutagenesis analysis suggested that the hydrophobic residue (I564) located in gp41 pocket-forming site is pivotal for anti-HIV activity of trilobatin. Furthermore, trilobatin displayed synergistic anti-HIV activities combined with Other antiretroviral agents. Trilobatin has a good potential to be developed as a small-molecule HIV-1 entry inhibitor for clinical combination therapy.

Keywords
HIV; HIV entry inhibitor; N-terminal heptad repeats; gp41 envelope; six-helix bundle; trilobatin.
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