Identification of human immunodeficiency virus type-1 Gag-TSG101 interaction inhibitors by high-throughput screening

被引：5

作者：

Siarot, Lowela ^{[1
,2
,3
]}

Chutiwitoonchai, Nopporn ^{[1
,2
]}

Sato, Hirotaka ^{[1
,2
]}

Chang, Hao ^{[1
,2
,4
]}

Sato, Hironori ^{[5
]}

Fujino, Masayuki ^{[6
]}

Murakami, Tsutomu ^{[6
]}

Aono, Toshihiro ^{[3
]}

Kodama, Eiichi ^{[7
,8
]}

Kuroda, Kazumichi ^{[9
]}

Takei, Masami ^{[9
]}

Aida, Yoko ^{[1
,2
,4
]}

机构：

[1] RIKEN, Nano Med Engn Lab, Cluster Pioneering Res, 2-1 Hirosawa, Wako, Saitama 3510198, Japan

[2] RIKEN, Viral Infect Dis Unit, 2-1 Hirosawa, Wako, Saitama 3510198, Japan

[3] Univ Tokyo, Biotechnol Res Ctr, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Frontier Sci, Lab Viral Infect Dis, Dept Med Genome Sci, Saitama, Japan

[5] Natl Inst Infect Dis, Pathogen Genom Ctr, Lab Viral Genom, Tokyo, Japan

[6] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan

[7] Tohoku Univ, Int Inst Disaster Sci, Div Infect Dis, Sendai, Miyagi, Japan

[8] Tohoku Univ, Tohoku Med Megabank Org, Sendai, Miyagi, Japan

[9] Nihon Univ, Sch Med, Tokyo, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2018年 / 503卷 / 04期

关键词：

HIV-1; Gag; TSG101; Gag-TSG101 interaction inhibitors; inhibitor; ELISA; High-throughput screening; TSG101; INFECTION; DOMAIN; RELEASE; MOTIFS;

D O I：

10.1016/j.bbrc.2018.08.079

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：

The interaction between viral protein Gag and cellular protein tumor susceptibility gene 101 (TSG101) is a crucial step in the HIV-1 replication cycle. This interaction initiates the viral assembly/budding via the cellular endosomal sorting complexes required for transport (ESCRT) pathway, making it a potential target for antiviral therapy. Here we developed a simple, robust, and reliable high-throughput screening (HTS) system based on enzyme-linked immunosorbent assay (ELISA) to identify compounds that inhibit HIV-1 replication by targeting Gag-TSG101 interaction. Through screening of the 9600-compound library using the established HTS system, several hit compounds, which inhibited Gag-TSG101 interaction, were identified. Subsequent assays revealed two hit compounds, HSM-9 and HSM-10, which have antiviral activity against CD4(+) T cell-tropic NL4-3 and macrophage-tropic JR-CSF HIV-1 strains. These results suggest that our established HTS system is an indispensable tool for the identification of HIV-1 Gag-TSG101 interaction inhibitors. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：2970 / 2976

页数：7

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