Antiviral Activity of CD437 Against Mumps Virus.

Fumihiro Kato,Toshiyuki Yamaji,Yuichiro Nakatsu,Hiroshi Katoh,Keiko Murano,Aika Wakata,Makoto Takeda,Minoru Kidokoro,Takayuki Hishiki,Toru Kubota

doi:10.3389/fmicb.2021.751909

Abstract

Many efforts have been dedicated to the discovery of antiviral drug candidates against the mumps virus (MuV); however, no specific drug has yet been approved. The development of efficient screening methods is a key factor for the discovery of antiviral candidates. In this study, we evaluated a screening method using an Aequorea coerulescens green fluorescent protein-expressing MuV infectious molecular clone. The application of this system to screen for active compounds against MuV replication revealed that CD437, a retinoid acid receptor agonist, has anti-MuV activity. The point of antiviral action was a late step(s) in the MuV life cycle. The replication of other paramyxoviruses was also inhibited by CD437. The induction of retinoic acid-inducible gene (RIG)-I expression is a reported mechanism for the antiviral activity of retinoids, but our results indicated that CD437 did not stimulate RIG-I expression. Indeed, we observed antiviral activity despite the absence of RIG-I, suggesting that CD437 antiviral activity does not require RIG-I induction.

Highlights

Mumps virus (MuV), of the genus Orthorubulavirus in the family Paramyxoviridae, has a worldwide circulation
We previously developed an Aequorea coerulescens green fluorescent protein (AcGFP)-expressing mumps virus (MuV) based on the Odate strain (Katoh et al, 2017)
To establish an efficient screening system using AcGFP-MuV, Huh7, Vero, A549/hSLAM, and A549/hSLAM interferonalpha/beta receptor subunit 1 (IFNAR1) KO cells were evaluated by Z factor, which is an important index for screening (Zhang et al, 1999)

Summary

Introduction

Mumps virus (MuV), of the genus Orthorubulavirus in the family Paramyxoviridae, has a worldwide circulation. Infection by MuV usually causes a mild or moderate disease with fever and swelling of the parotid gland, but is occasionally associated with serious complications such as aseptic meningitis and hearing loss (Hviid et al, 2008). Mumps vaccines are effective against MuV infection and are widely used, especially in developed countries. Recurrent outbreaks have occurred in several countries despite their common use of mumps vaccines (Watson-Creed et al, 2006; Kutty et al, 2014; Rubin et al, 2016; Su et al, 2020). Treatment for MuV infection mainly focuses on alleviating the symptoms (McLean et al, 1964; Trojian et al, 2009)

Methods

Results

Conclusion