Rosmarinic acid inhibits Rift Valley fevervirus: in vitro, computational and analyticalstudies: supplementary materials

Aim: The antiviral potentials of rosmarinic acid (RA) against Rift Valley fever (RVF) virus were investigated.Methods: Antiviral activity was investigated by evaluating the reduction in the viral infectivity titer.Computational and LC–MS studies were performed for investigating the mechanism of action. This isvia testing the interaction between RA and its major metabolite with the key infectivity proteins anddetermination of RA cellular permeability. Results: A superior reduction in RVF infectivity titer (45.5%)was observed when RA was applied post-infection compared to 17.7% reduction following its applicationbefore infection in addition to time-dependent inactivation kinetics. Recorded data showed in-silicoinhibitory potential of RA and its metabolite against RVFV cap-binding protein and glycoprotein C, whichare integral for viral transcription. LC–MS revealed cellular inclusion of RA, supporting its intracellularviral interaction. Conclusion: These antiviral potentials might suggest a promising foundation for futureanti-RVF drug development.

研究目的：探讨迷迭香酸（rosmarinic acid, RA）针对裂谷热（Rift Valley fever, RVF）病毒的抗病毒潜能。研究方法：通过评估病毒感染性滴度的降幅探究其抗病毒活性；开展计算生物学与液相色谱-质谱联用（LC–MS）研究，通过检测迷迭香酸及其主要代谢产物与关键感染性蛋白的相互作用，并测定迷迭香酸的细胞通透性，以阐明其作用机制。研究结果：与感染前给药仅17.7%的病毒滴度降幅相比，感染后给药时迷迭香酸可使RVF病毒感染性滴度降低45.5%，降幅更为显著，同时呈现出时间依赖性的灭活动力学特征。硅基模拟（in-silico）实验数据显示，迷迭香酸及其代谢产物对RVFV帽结合蛋白与糖蛋白C具有抑制活性，而这两类蛋白是病毒转录过程不可或缺的关键组分。液相色谱-质谱联用检测结果证实，迷迭香酸可被细胞摄取，为其胞内抗病毒相互作用提供了佐证。研究结论：上述抗病毒活性可为未来抗裂谷热病毒药物的研发提供颇具前景的理论基础。