TY - JOUR
T1 - Identification of human immunodeficiency virus type-1 Gag-TSG101 interaction inhibitors by high-throughput screening
AU - Siarot, Lowela
AU - Chutiwitoonchai, Nopporn
AU - Sato, Hirotaka
AU - Chang, Hao
AU - Sato, Hironori
AU - Fujino, Masayuki
AU - Murakami, Tsutomu
AU - Aono, Toshihiro
AU - Kodama, Eiichi
AU - Kuroda, Kazumichi
AU - Takei, Masami
AU - Aida, Yoko
N1 - Funding Information:
We thank the Platform for Drug Discovery, Informatics, and Structural Life Science of the Ministry of Education, Culture, Sports, Science and Technology, Japan for providing the chemical compound library. We are grateful to Dr. A. Adachi (Tokushima University) for providing the pNL4-3; Dr. Y. Koyanagi (Kyoto University) for providing pYKJR-CSF; Dr. Y Maeda, (Kumamoto University) for providing PM1/CCR5 cells; Dr. H. Otsuki (RIKEN) for his suggestions on the infection experiment; and Mr. S. Matsuyama (National Institute of Infectious Diseases) for his excellent technical assistance. We also thank the RIKEN BSI Research Resource Center for the DNA sequencing analysis. This study was partly supported by a grant to HS and YA (Research on HIV/AIDS project no. H22-003) from the Ministry of Health, Labour and Welfare of Japan, and by a grant to HS and YA (Research on HIV/AIDS project no. 16fk0410104j0001) from the Japan Agency for Medical Research and Development.
Funding Information:
We thank the Platform for Drug Discovery, Informatics, and Structural Life Science of the Ministry of Education, Culture, Sports, Science and Technology, Japan for providing the chemical compound library. We are grateful to Dr. A. Adachi (Tokushima University) for providing the pNL4-3; Dr. Y. Koyanagi (Kyoto University) for providing pYKJR-CSF; Dr. Y Maeda, (Kumamoto University) for providing PM1/CCR5 cells; Dr. H. Otsuki (RIKEN) for his suggestions on the infection experiment; and Mr. S. Matsuyama (National Institute of Infectious Diseases) for his excellent technical assistance. We also thank the RIKEN BSI Research Resource Center for the DNA sequencing analysis. This study was partly supported by a grant to HS and YA (Research on HIV/AIDS project no. H22-003 ) from the Ministry of Health, Labour and Welfare of Japan , and by a grant to HS and YA (Research on HIV/AIDS project no. 16fk0410104j0001 ) from the Japan Agency for Medical Research and Development .
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9/18
Y1 - 2018/9/18
N2 - 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.
AB - 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.
KW - ELISA
KW - Gag-TSG101 interaction inhibitors
KW - HIV-1 Gag
KW - HIV-1 inhibitor
KW - High-throughput screening
KW - TSG101
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U2 - 10.1016/j.bbrc.2018.08.079
DO - 10.1016/j.bbrc.2018.08.079
M3 - Article
C2 - 30126636
AN - SCOPUS:85051630031
SN - 0006-291X
VL - 503
SP - 2970
EP - 2976
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
