1. A heterocyclic compound inhibits viral release by inducing cell surface BST2/Tetherin/CD317/HM1.24.
- Author
-
Nyame P, Togami A, Yoshida T, Masunaga T, Begum MM, Terasawa H, Monde N, Tahara Y, Tanaka R, Tanaka Y, Appiah-Kubi J, Amesimeku WAO, Hossain MJ, Otsuka M, Yoshimura K, Ikeda T, Sawa T, Satou Y, Fujita M, Maeda Y, Tateishi H, and Monde K
- Subjects
- Humans, Jurkat Cells, HIV Infections drug therapy, HIV Infections virology, HIV Infections metabolism, Heterocyclic Compounds pharmacology, Anti-HIV Agents pharmacology, Simian Immunodeficiency Virus drug effects, SARS-CoV-2 drug effects, SARS-CoV-2 metabolism, Bone Marrow Stromal Antigen 2, GPI-Linked Proteins metabolism, GPI-Linked Proteins genetics, Antigens, CD metabolism, Antigens, CD genetics, HIV-1 drug effects, Virus Release drug effects
- Abstract
The introduction of combined antiretroviral therapy (cART) has greatly improved the quality of life of human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, the ever-present desire to seek out a full remedy for HIV-1 infections makes the discovery of novel antiviral medication compelling. Owing to this, a new late-stage inhibitor, Lenacapavir/Sunlenca, an HIV multi-phase suppressor, was clinically authorized in 2022. Besides unveiling cutting-edge antivirals inhibiting late-stage proteins or processes, newer therapeutics targeting host restriction factors hold promise for the curative care of HIV-1 infections. Notwithstanding, bone marrow stromal antigen 2 (BST2)/Tetherin/CD317/HM1.24, which entraps progeny virions is an appealing HIV-1 therapeutic candidate. In this study, a novel drug screening system was established, using the Jurkat/Vpr-HiBiT T cells, to identify drugs that could obstruct HIV-1 release; the candidate compounds were selected from the Ono Pharmaceutical compound library. Jurkat T cells expressing Vpr-HiBiT were infected with NL4-3, and the amount of virus release was quantified indirectly by the amount of Vpr-HiBiT incorporated into the progeny virions. Subsequently, the candidate compounds that suppressed viral release were used to synthesize the heterocyclic compound, HT-7, which reduces HIV-1 release with less cellular toxicity. Notably, HT-7 increased cell surface BST2 coupled with HIV-1 release reduction in Jurkat cells but not Jurkat/KO-BST2 cells. Seemingly, HT-7 impeded simian immunodeficiency virus (SIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) release. Concisely, these results suggest that the reduction in viral release, following HT-7 treatment, resulted from the modulation of cell surface expression of BST2 by HT-7., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF