Abstract
Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In this study, we exhibited the antiviral activity of amentoflavone, a naturally occurring biflavonoid, toward HSV-1 and ACV-resistant strains. Amentoflavone significantly inhibited infection of HSV-1 (F strain), as well as several ACV-resistant strains including HSV-1/106, HSV-1/153 and HSV-1/Blue at high concentrations. Time-of-drug-addition assay further revealed that amentoflavone mainly impaired HSV-1 early infection. More detailed study demonstrated that amentoflavone affected cofilin-mediated F-actin reorganization and reduced the intracellular transportation of HSV-1 from the cell membrane to the nucleus. In addition, amentoflavone substantially decreased transcription of viral immediate early genes. Collectively, amentoflavone showed strong antiviral activity against HSV-1 and ACV-resistant strains, and amentoflavone could be a promising therapeutic candidate for HSV-1 pathogenesis.
Highlights
Herpes Simplex Virus type 1 (HSV-1) is a DNA virus with envelope and belongs to α subfamilyHerpesviridae [1]
We evaluated whether amentoflavone can inhibit Herpes simplex virus 1 (HSV-1) infection and revealed the mechanism thereof
The antiviral activity of amentoflavone was estimated by cytopathic effects (CPEs) and plaque assay, respectively, which showed that amentoflavone inhibited HSV-1 infection in a dose-dependent manner (Figure 1E,F)
Summary
Herpes Simplex Virus type 1 (HSV-1) is a DNA virus with envelope and belongs to α subfamilyHerpesviridae [1]. Herpes Simplex Virus type 1 (HSV-1) is a DNA virus with envelope and belongs to α subfamily. HSV-1 can cause a variety of clinical disorders, such as encephalitis and keratitis, and importantly, the mortality rate of HSV-1-induced encephalitis is about 70% [2]. HSV-1 establishes latent infection in peripheral nerve ganglia and the central nervous system, and the latent virus can be reactivated under psychological stress [3]. Further increasing evidences indicate that HSV-1 infection plays a role in the development of neurodegeneration disease, such Alzheimer’s disease [4]. The clinically therapeutic drug against HSV-1 infection is Acyclovir (ACV), a nucleoside analog that has been hailed as a milestone in the history of antiviral drugs [5]. ACV-resistant viruses appear gradually [6], making developing novel and high-efficiency antiviral agents important
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