Broad-spectrum antiviral activity of the sigma-1 receptor antagonist PB28 against coronaviruses

文献类型： 外文期刊

第一作者： Song, Gaojie

作者： Song, Gaojie;Cheng, Lingling;Cheng, Lingling;Cheng, Jia;Dong, Xingpeng;Li, Dapeng;Shang, Chao;Li, Xiao;Zhang, Cuiling;Zhu, Ran;Li, Junwei

作者机构：

关键词： coronavirus; PB28; sigma-1 receptor; antiviral activity; animal models

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：4.5； 五年影响因子：5.2 ）

ISSN：

年卷期： 2025 年 16 卷

页码：

收录情况： SCI

摘要： The continuous evolution of coronaviruses poses persistent and severe threats to both human and animal health. While alpha- and beta-coronaviruses mainly infect mammals, including humans, gamma-coronaviruses predominantly infect poultry, causing substantial economic losses. Their rapid mutation rates and wide host tropism underscore the urgent demand for pan-coronavirus therapeutics. Here, we systematically investigated the antiviral potency and mechanism of action of PB28, a selective sigma-1 receptor antagonist, across alpha-, beta-, and gamma-coronaviruses. Molecular docking predicted a stable interaction between PB28 and the sigma-1 receptor. PB28 exhibits robust in vitro antiviral activity, effectively inhibiting the replication of beta-coronaviruses (SARS-CoV-2 and its Beta, Delta, and Omicron variants; HCoV-OC43), alpha-coronaviruses (PEDV and TGEV), and gamma-coronaviruses (IBV). Broad-spectrum antiviral efficacy is further validated by viral titration assays. In vivo, PB28 administration in K18-hACE2 mice infected with SARS-CoV-2 Delta and BALB/c mice infected with HCoV-OC43 led to significantly reduced viral loads, attenuated multi-organ pathology, and improved survival and body weight maintenance. In parallel, PB28 treatment in IBV-infected chicken embryos and neonatal chicks enhanced survival, supported embryogenesis, and alleviated tissue damage. Collectively, PB28 demonstrates cross-genus antiviral efficacy, likely mediated through modulation of the sigma-1 receptor. These findings highlight PB28 as a promising lead compound for the development of pan-coronavirus therapeutics.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序