HIV-1 Resistance Mechanism to an Electrostatically Constrained Peptide Fusion Inhibitor That Is Active against T-20-Resistant Strains

被引：4

作者：

Shimane, Kazuki ^{[1
]}

Kawaji, Kumi ^{[2
]}

Miyamoto, Fusako ^{[2
]}

Oishi, Shinya ^{[4
]}

Watanabe, Kentaro ^{[4
]}

Sakagami, Yasuko ^{[1
]}

Fujii, Nobutaka ^{[4
]}

Shimura, Kazuya ^{[1
]}

Matsuoka, Masao ^{[1
]}

Kaku, Mitsuo ^{[3
]}

Sarafianos, Stefan G. ^{[5
,6
]}

Kodama, Eiichi N. ^{[1
,2
,3
]}

机构：

[1] Kyoto Univ, Inst Virus Res, Lab Virus Control, Kyoto 606, Japan

[2] Tohoku Med Megabank Org, Sendai, Miyagi, Japan

[3] Tohoku Univ, Sch Med, Dept Internal Med, Div Infect Control & Lab Diagnost, Sendai, Miyagi 980, Japan

[4] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto, Japan

[5] Univ Missouri, Sch Med, Christopher S Bond Life Sci Ctr, Columbia, MO USA

[6] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2013年 / 57卷 / 08期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; TERMINAL HEPTAD REPEAT; ENFUVIRTIDE RESISTANCE; MUTATIONS; GP41; SENSITIVITY; DESIGN; IMPACT; ENTRY; EMERGENCE;

D O I：

10.1128/AAC.00237-13

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

T-20EK is a novel fusion inhibitor designed to have enhanced alpha-helicity over T-20 (enfuvirtide) through engineered electrostatic interactions between glutamic acid (E) and lysine (K) substitutions. T-20EK efficiently suppresses wild-type and T-20-resistant variants. Here, we selected T-20EK-resistant variants. A combination of L33S and N43K substitutions in gp41 were required for high resistance to T-20EK. While these substitutions also caused resistance to T-20, they did not cause cross-resistance to other known fusion inhibitors.

引用

页码：4035 / 4038

页数：4

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