1. A potential anti-HIV-1 compound, Q308, inhibits HSV-2 infection and replication in vitro and in vivo.
- Author
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Zhang, Xin, Li, Axin, Li, Ting, Shou, Zeren, Li, Yibin, Qiao, Xinman, Zhou, Ruijing, Zhong, Xuelin, Li, Songshan, and Li, Lin
- Subjects
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HERPES genitalis , *VIRAL proteins , *CYTOKINE release syndrome , *VIRUS diseases , *PROTEIN synthesis , *TITERS - Abstract
HSV-2 is a common human pathogen worldwide that causes genital herpes. Due to the lack of an effective HSV-2 vaccine in the foreseeable future, there is an urgent need to develop effective, safe and affordable anti-HSV-2 agents. Our previous studies confirmed that a small-molecule compound, Q308, effectively inhibits the reactivation of latent HIV and might be developed as an anti-HIV-1 agent. Patients infected with HSV-2 are generally more susceptible to HIV-1 infection than normal humans. In this study, we found that Q308 treatment had strong inhibitory activity against both HSV-2 and acyclovir-resistant HSV-2 strains in vitro and reduced the viral titers in tissue. And this treatment effectively ameliorated the cytokine storm and pathohistological changes caused by HSV-2 infection in HSV-2-infected mice. Unlike nucleoside analogs such as acyclovir, Q308 inhibited post-viral entry events by attenuating the synthesis of viral proteins. Furthermore, Q308 treatment blocked HSV-2-induced PI3K/AKT phosphorylation due to its inhibition on viral infection and replication. Overall, Q308 treatment exhibits potent anti-HSV-2 activity by inhibiting viral replication both in vitro and in vivo. Q308 is a promising lead compound for the development of new anti-HSV-2/HIV-1 therapies, particularly against acyclovir-resistant HSV-2 strains. [Display omitted] • A potential anti-HIV-1 compound, Q308, inhibited HSV-2 infection and replication. • Q308 inhibited post-viral entry by blocking the synthesis of viral proteins. • Q308 treatment affected HSV-2-induced PI3K/AKT phosphorylation. • Q308 is a lead compound for the development of a new anti-HSV-2/HIV-1 agent. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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