ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1664973
Early Boosting of p38 MAPK Signaling Pathway by Lycorine Hydrochloride Potently Inhibits PRRSV Proliferation in Primary and Established Cells
Provisionally accepted
Lizhan Su1Zhening Zhang1Siqi Zhang1Jiajing He1
Yaoqi Chen1Guohong Wu1Zhiying Zhang1Weisan Chen2Mingxin Zhang3
Jianxin Chen1*- 1South China Agricultural University, Guangzhou, China
- 2La Trobe University, Melbourne, Australia
- 3Wuyi University, Jiangmen, China
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Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous economic losses in the swine industry since emerging in the late 1980s. Although vaccination has been widely used to control PRRS epidemics in Chinese pig farms, they provided limited protection against PRRSV transmission; moreover, no effective therapeutic drugs are available. Therefore, there is an urgent need to develop novel antiviral strategies to control PRRSV epidemics. This study showed that Lycorine hydrochloride (LH), an isoquinoline alkaloid isolated from the bulb of Lycoris radiata herb, potently suppressed PRRSV replication in Marc-145 cells and primary porcine alveolar macrophages ex vivo (PAMs) with 50% effective antiviral concentrations (EC50) less than 1 µM. LH exhibited broadspectrum inhibitory activities in vitro against clinically circulating type 2 PRRSV GD-HD, CH-1a, and NADC30-like HNhx strains in China. Mechanistically, LH treatment induced a rapid up-regulation of p38 MAPK signaling pathway in both infected and uninfected cells, which enhanced the expressions of NLRP3 and Caspase-1 proteins, thereby promoting the conversion of pro-IL-1β to IL-1β, which led to decreased PRRSV replication. In summary, this study reveals that early boosting of p38 MAPK signaling pathway induced by LH treatment significantly suppresses PRRSV propagation, and LH has the potential to be used as a novel antiviral agent against PRRSV infections.
Keywords: Porcine reproductive and respiratory syndrome virus (PRRSV), Lycorine hydrochloride (LH), p38 mitogen-activated protein kinase (p38 MAPK), NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3), Interleukin-1β (IL-1β)
Received: 13 Jul 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Su, Zhang, Zhang, He, Chen, Wu, Zhang, Chen, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jianxin Chen, South China Agricultural University, Guangzhou, China
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