Verapamil inhibits respiratory syncytial virus infection by regulating Ca2+ influx

• Published in: Life sciences (1973) 2024-09, Vol.352, p.122877, Article 122877
• Main Authors: Chen, Fang, Shen, Huyan, Liu, Gang, Zhang, Pingping, Zhang, Lin, Lin, Siyu, Gao, Han, Peng, Hong, Qi, Yan-Fei, Chen, Yan, Jiang, Yinhui, Huang, Jiandong, Shen, Xiangchun, Luo, Yu-Si, Zhang, Ke
• Format: Article
• Language: English
• Subjects: Anti-virus; Ca2; EGTA; Respiratory syncytial virus; Verapamil
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2024.122877

The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.