2. Academic Validation
  3. A potential anti-HIV-1 compound, Q308, inhibits HSV-2 infection and replication in vitro and in vivo

A potential anti-HIV-1 compound, Q308, inhibits HSV-2 infection and replication in vitro and in vivo

  • Biomed Pharmacother. 2023 Mar 27;162:114595. doi: 10.1016/j.biopha.2023.114595.
Xin Zhang 1,  Axin Li 1,  Ting Li 2,  Zeren Shou 1,  Yibin Li 1,  Xinman Qiao 1,  Ruijing Zhou 1,  Xuelin Zhong 1,  Songshan Li 1,  Lin Li 3
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 2 Aviation Hygiene Management Division, China Southern Airlines Company Limited, Guangzhou 510406, China.
  • 3 NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: li75lin@smu.edu.cn.
PMID: 36989723 DOI: 10.1016/j.biopha.2023.114595
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.

Keywords

Acyclovir-resistant HSV-2 strain; HSV-2; HSV-2/HIV-1 coinfection; Q308.

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