Antiviral activity of triptolide on herpes simplex virus in vitro

Immun Inflamm Dis. 2022 Jul;10(7):e667. doi: 10.1002/iid3.667.

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

Keywords: HSV-1; ICP4; antiviral; natural product; triptolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Chlorocebus aethiops
  • Diterpenes* / metabolism
  • Diterpenes* / pharmacology
  • Epoxy Compounds
  • Herpes Simplex* / drug therapy
  • Herpesvirus 1, Human*
  • Humans
  • Infant, Newborn
  • Phenanthrenes
  • Vero Cells

Substances

  • Antiviral Agents
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • triptolide