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

文献类型： 外文期刊

作者： Song, Gaojie 1 ; Cheng, Lingling 1 ; Dong, Xingpeng 3 ; Li, Dapeng 4 ; Cheng, Jia 2 ; Shang, Chao 5 ; Li, Xiao 5 ; Zhu, Ran 6 ; Zhang, Cuiling 5 ; Li, Junwei 7 ;

作者机构： 1.Jiujiang Univ, Sch Basic Med Sci, Jiangxi Prov Key Lab Cell Precis Therapy, Jiujiang, Peoples R China

2.Jiujiang Univ, Affiliated Hosp 2, Jiujiang, Peoples R China

3.Nantong Univ, Sch Pharm, Nantong, Peoples R China

4.First Hosp Jilin Univ, Dept Neurosurg, Changchun, Peoples R China

5.Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun, Peoples R China

6.Yanbian Univ, Coll Med, Yanji, Peoples R China

7.Nanjing Univ Chinese Med, Hosp Nanjing 2, Dept Infect Dis, Nanjing, Peoples R China

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.

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