Antiviral activity of arbidol hydrochloride against herpes simplex virus I in vitro and in vivo

Int J Antimicrob Agents. 2018 Jan;51(1):98-106. doi: 10.1016/j.ijantimicag.2017.09.001. Epub 2017 Sep 7.

Abstract

Herpes simplex virus type 1 (HSV-1) causes significant human diseases ranging from skin lesions to encephalitis, especially in neonates and immunocompromised hosts. The discovery of novel anti-HSV-1 drugs with low toxicity is required for public health. Arbidol hydrochloride (ARB) is an indole derivative molecule with broad-spectrum antiviral activity. In this study, the antiviral effects of ARB against HSV-1 infection were evaluated in vitro and in vivo. The results showed that ARB presents significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with EC50 values (50% effective concentration) of 5.39 µg/mL (10.49 µM) and 2.26 µg/mL (4.40 µM), respectively. Moreover, time-of-addition and time-of-removal assays further suggested that ARB has viral inhibitory effects when added up to 12 h post-infection (p.i.), which could be further corroborated by determining the expression of viral immediate-early (ICP4, ICP22 and ICP27), early (ICP8 and UL42) and late (gB, gD, gH, VP1/2 and VP16) genes by real-time quantitative PCR as well as the expression of viral protein ICP4 and ICP8 at 6 h and 12 h p.i. Results of the in vivo study showed that ARB could reduce guinea pig skin lesions caused by HSV-1 infection. Conclusively, this report offers new perspectives in the search for therapeutic measures in the treatment of HSV-1 infection.

Keywords: Antiviral; Arbidol hydrochloride; HSV-1.

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Guinea Pigs
  • HeLa Cells
  • Herpes Simplex / drug therapy*
  • Herpesvirus 1, Human / drug effects*
  • Humans
  • Immediate-Early Proteins / biosynthesis
  • Immediate-Early Proteins / genetics
  • Indoles / therapeutic use*
  • Skin / pathology
  • Skin / virology
  • Skin Diseases, Viral* / drug therapy
  • Skin Diseases, Viral* / veterinary
  • Skin Diseases, Viral* / virology
  • Vero Cells
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • DNA-Binding Proteins
  • ICP8 protein, Simplexvirus
  • Immediate-Early Proteins
  • Indoles
  • Viral Proteins
  • herpes simplex virus IE3 protein, Human herpesvirus 1
  • umifenovir