Department of Clinical Virology, Clinical Microbiology Research Center, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroder Arthritis Institute, University Health Network, Toronto, Canada.
Immun Inflamm Dis. 2022 Jul;10(7):e667. doi: 10.1002/iid3.667.
Herpes simplex virus-type 1 (HSV-1) can cause diseases, especially amongst neonates and immunocompromised hosts. Hence, developing a novel anti-HSV-1 drug with low-level toxicity is vital. Triptolide (TP), a diterpenoid triepoxide is a natural product with range of bioactivity qualities.
In this study, viral infection was assessed in different phases of the HSV-1 replication cycle on A549 cells, using various assays, such as adsorption inhibition assay, penetration inhibition assay, time-of-addition assay, and quantitative polymerase chain reaction (qPCR).
The results indicate that TP can effectively inhibit HSV-1 infection in the lowest range of concentration. TP exhibited significant inhibitory effect on HSV-1 plaque formation, with 50% effective concentration (EC50) of 0.05 µM. Furthermore, the time-of-addition assay suggests that TP has viral inhibitory effects when it was added less than 8 h postinfection (h.p.i.). This result is further confirmed by decline in the expression viral immediate-early genes (ICP4, ICP22, and ICP27) in 6 h.p.i in the TP-treated group compared to the control group, evaluated by real-time qPCR. The Western blotting result was also consistent with the previous findings, which confirms that TP can positively affect ICP4 during HSV-1 infection.
The TP also showed antiviral activity against HSV-1. This dose-dependent activity is an indication of a particular cellular component, rather than cytotoxicity that has mediated its function. Finally, the result suggest a new approach for an effective treatment option of the HSV-1 infections.
单纯疱疹病毒 1 型（HSV-1）可引起疾病，尤其是在新生儿和免疫功能低下的宿主中。因此，开发一种毒性低的新型抗 HSV-1 药物至关重要。雷公藤红素（TP）是一种二萜三环氧天然产物，具有多种生物活性。
本研究采用吸附抑制试验、渗透抑制试验、时效试验和实时定量聚合酶链反应（qPCR）等方法，在 A549 细胞中评估 HSV-1 复制周期的不同阶段的病毒感染。
结果表明，TP 可在最低浓度范围内有效抑制 HSV-1 感染。TP 对 HSV-1 蚀斑形成表现出显著的抑制作用，半数有效浓度（EC50）为 0.05μM。此外，时效试验表明，TP 在感染后少于 8 小时（h.p.i.）加入时具有抗病毒作用。这一结果通过实时 qPCR 进一步证实，与对照组相比，TP 处理组在 6 h.p.i.时病毒即刻早期基因（ICP4、ICP22 和 ICP27）的表达下降。Western blot 结果也与上述发现一致，证实 TP 可在 HSV-1 感染过程中对 ICP4 产生积极影响。
TP 还显示出对 HSV-1 的抗病毒活性。这种剂量依赖性活性表明其作用是针对特定的细胞成分，而不是介导其功能的细胞毒性。最后，结果提示了一种治疗 HSV-1 感染的新方法。
