2. Academic Validation
  3. Trilobatin as an HIV-1 entry inhibitor targeting the HIV-1 Gp41 envelope

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

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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