Meclizine Inhibits Pseudorabies Virus Replication by Interfering With Virus Entry and Release.

Norbert Nowotny,Panrao Liu,Zhengmin Lian,Zhenbang Zhu,Xiaohui Yao,Lili Yuan,Yi Shi,Danhe Hu,Xiangdong Li

doi:10.3389/fmicb.2021.795593

Abstract

Pseudorabies virus (PRV) is a pathogen that causes substantial economic losses to the swine industry. With the emergence and widespread of PRV variants since 2011 in China, current commercial vaccines cannot provide complete protection against PRV infection. Therefore, antiviral drugs may work as an alternative way to control and prevent PRV. In this study, the inhibitory effects and underlying molecular mechanisms of meclizine against PRV were studied. Meclizine displayed a significant inhibitory effect against PRV when it was added before, simultaneously with, or after virus infection. The inhibitory effect of meclizine occurred during viral entry and cell-to-cell spreading but not at viral attachment into PK-15 cells. Meclizine also inhibited viral particle release at the late stage of infection. The antiviral effect of meclizine was tested in mice, and the results showed that meclizine reduced the severity of clinical symptoms and the viral loads in tissues, and delayed the death, after PRV challenge. The above results indicated that meclizine had an inhibitory effect on PRV. Our findings will contribute to the development of potential therapeutic drugs against PRV infection.

Highlights

Pseudorabies (PR) is an acute highly contagious disease caused by pseudorabies virus (PRV)
To evaluate the antiviral activity of meclizine against PRV infection, we first investigated its cytotoxicity on PK-15 cells
We for the first time verified that meclizine had potent inhibitory effect on PRV variant strain and Bartha K61 strain both in vitro and in vivo

Summary

Introduction

Pseudorabies (PR) is an acute highly contagious disease caused by pseudorabies virus (PRV). It was first described in Hungary in 1902 (Lee and Wilson, 1979). PRV, an enveloped and double-stranded linear DNA virus, is a member of the Herpesviridae family (Sun et al, 2016). It was called Aujeszky’s disease virus (ADV), which causes fever, itching (except pigs), and encephalomyelitis in many livestock and wild animals (Müller et al, 2011; Tan et al, 2021). PRV can infect pigs of different ages. It has been reported that PRV infects and causes human endophthalmitis or Meclizine Inhibits the Entry and Release of PRV encephalitis, which highlights the potential threat of this pathogen to public health (Wong et al, 2019; Yang et al, 2019; Liu et al, 2020)

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Conclusion