Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 503, Issue 4, Pages 2970-2976Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.08.079
Keywords
HIV-1 Gag; TSG101; Gag-TSG101 interaction inhibitors; HIV-1 inhibitor; ELISA; High-throughput screening
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Funding
- Ministry of Health, Labour and Welfare of Japan [H22-003]
- Japan Agency for Medical Research and Development [16fk0410104j0001]
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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.
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