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Int J Antimicrob Agents ; 51(1): 98-106, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28890393

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.


Subject(s)
Antiviral Agents/therapeutic use , Herpes Simplex/drug therapy , Herpesvirus 1, Human/drug effects , Indoles/therapeutic use , Skin Diseases, Viral , Animals , Cell Line, Tumor , Chlorocebus aethiops , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Guinea Pigs , HeLa Cells , Humans , Immediate-Early Proteins/biosynthesis , Immediate-Early Proteins/genetics , 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
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