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

被引：26
作者：
Yin, Shuwen [1 ]
Zhang, Xuanxuan [1 ]
Lai, Fangyuan [1 ]
Liang, Taizhen [1 ]
Wen, Jiayong [1 ]
Lin, Wanying [1 ]
Qiu, Jiayin [2 ]
Liu, Shuwen [1 ]
Li, Lin [1 ]
机构：
[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangzhou, Guangdong, Peoples R China
[2] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China
来源：
FEBS LETTERS | 2018年 / 592卷 / 13期
关键词：
gp41; envelope; HIV; HIV entry inhibitor; N-terminal heptad repeats; six-helix bundle; trilobatin; ANTIVIRAL ACTIVITY; FUSION INHIBITORS; IDENTIFICATION; MICROBICIDE; COAGULATION; DERIVATIVES; FLAVONOIDS; OVALBUMIN; PEPTIDES; DESIGN;
D O I：
10.1002/1873-3468.13113
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 (1564) 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.
引用
收藏
页码：2361 / 2377
页数：17
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