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

Lowela Siarot, Nopporn Chutiwitoonchai, Hirotaka Sato, Hao Chang, Hironori Sato, Masayuki Fujino, Tsutomu Murakami, Toshihiro Aono, Eiichi Kodama, Kazumichi Kuroda, Masami Takei, Yoko Aida

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2970-2976
Number of pages7
JournalBiochemical and biophysical research communications
Volume503
Issue number4
DOIs
Publication statusPublished - 2018 Sep 18

Keywords

  • ELISA
  • Gag-TSG101 interaction inhibitors
  • HIV-1 Gag
  • HIV-1 inhibitor
  • High-throughput screening
  • TSG101

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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