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

页码：2361 / 2377

页数：17

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