Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the modification of membrane fluidity

  • Biochem Biophys Res Commun. 2015 Feb 13;457(3):288-94. doi: 10.1016/j.bbrc.2014.12.102.
Kouki Matsuda  1 Shinichiro Hattori  1 Ryusho Kariya  1 Yuji Komizu  2 Eriko Kudo  1 Hiroki Goto  1 Manabu Taura  1 Ryuichi Ueoka  2 Shinya Kimura  3 Seiji Okada  4
Affiliations
  • 1. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
  • 2. Division of Applied Life Science, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
  • 3. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
  • 4. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan. Electronic address: [email protected].
Abstract

Membrane fusion between host cells and HIV-1 is the initial step in HIV-1 Infection, and plasma membrane fluidity strongly influences infectivity. In the present study, we demonstrated that GUT-70, a natural product derived from Calophyllum brasiliense, stabilized plasma membrane fluidity, inhibited HIV-1 entry, and down-regulated the expression of CD4, CCR5, and CXCR4. Since GUT-70 also had an inhibitory effect on viral replication through the inhibition of NF-κB, it is expected to be used as a dual functional and viral mutation resistant reagent. Thus, these unique properties of GUT-70 enable the development of novel therapeutic agents against HIV-1 Infection.

Keywords
Cell fusion; GUT-70; HIV-1 infection; Membrane fluidity; Viral entry.
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