Inhibition of Orbivirus Replication by Aurintricarboxylic Acid.

Celia Alonso,Sergio Utrilla-Trigo,Aitor Nogales,Eva Calvo-Pinilla,Javier Ortego,Luis Jiménez-Cabello

doi:10.3390/ijms21197294

Abstract

Bluetongue virus (BTV) and African horse sickness virus (AHSV) are vector-borne viruses belonging to the Orbivirus genus, which are transmitted between hosts primarily by biting midges of the genus Culicoides. With recent BTV and AHSV outbreaks causing epidemics and important economy losses, there is a pressing need for efficacious drugs to treat and control the spread of these infections. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antiviral activity. Here, we evaluated ATA as a potential antiviral compound against Orbivirus infections in both mammalian and insect cells. Notably, ATA was able to prevent the replication of BTV and AHSV in both cell types in a time- and concentration-dependent manner. In addition, we evaluated the effect of ATA in vivo using a mouse model of infection. ATA did not protect mice against a lethal challenge with BTV or AHSV, most probably due to the in vivo effect of ATA on immune system regulation. Overall, these results demonstrate that ATA has inhibitory activity against Orbivirus replication in vitro, but further in vivo analysis will be required before considering it as a potential therapy for future clinical evaluation.

Highlights

Viruses of the Orbivirus genus in the Reoviridae family are non-enveloped with an icosahedral capsid formed by three concentric protein layers, enclosing a double-stranded viral RNA genome formed by 10 segments [1,2]
Before examining the inhibitory effect of aurintricarboxylic acid (ATA) (Figure 1) against Bluetongue virus (BTV) or African horse sickness virus (AHSV) infection, we first determined the toxicity of ATA in Vero cells (Figure 2a)
To determine the therapeutic activity of ATA, Vero cells were infected with BTV-4 or AHSV-4 using a multiplicity of infection (MOI) of 0.01

Summary

Introduction

Viruses of the Orbivirus genus in the Reoviridae family are non-enveloped with an icosahedral capsid formed by three concentric protein layers, enclosing a double-stranded viral RNA genome formed by 10 segments [1,2]. Orbiviruses can infect a wide host range, such as ruminants, equids, camelids, marsupials, sloths, seabirds, bats, snakes, and in some cases humans [5,6,7,8,9]. BTV has a very wide distribution and can cause a severe hemorrhagic disease in ruminants, principally in sheep [10,11,12,13,14]. AHSV causes acute disease in equids, where mortality can reach 90% in susceptible horses [22,23,24]. There are nine serotypes distributed mostly in Sub-saharan Africa, cases have been reported in Asia and southern Europe [23,25,26]

Methods

Results

Conclusion