The broad-spectrum antiviral drug arbidol inhibits foot-and-mouth disease virus genome replication.

Morgan R Herod,Nicola J Stonehouse,Stephen J Polyak,Kirsten Bentley,Joseph Ward,Mark Harris,Oluwapelumi O Adeyemi

doi:10.1099/jgv.0.001283

Abstract

Arbidol (ARB, also known as umifenovir) is used clinically in several countries as an anti-influenza virus drug. ARB inhibits multiple enveloped viruses in vitro and the primary mode of action is inhibition of virus entry and/or fusion of viral membranes with intracellular endosomal membranes. ARB is also an effective inhibitor of non-enveloped poliovirus types 1 and 3. In the current report, we evaluate the antiviral potential of ARB against another picornavirus, foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus and an important veterinary pathogen. ARB inhibits the replication of FMDV RNA sub-genomic replicons. ARB inhibition of FMDV RNA replication is not a result of generalized inhibition of cellular uptake of cargo, such as transfected DNA, and ARB can be added to cells up to 3 h post-transfection of FMDV RNA replicons and still inhibit FMDV replication. ARB prevents the recovery of FMDV replication upon withdrawal of the replication inhibitor guanidine hydrochloride (GuHCl). Although restoration of FMDV replication is known to require de novo protein synthesis upon GuHCl removal, ARB does not suppress cellular translation or FMDV internal ribosome entry site (IRES)-driven translation. ARB also inhibits infection with the related Aphthovirus, equine rhinitis A virus (ERAV). Collectively, the data demonstrate that ARB can inhibit some non-enveloped picornaviruses. The data are consistent with inhibition of picornavirus genome replication, possibly via the disruption of intracellular membranes on which replication complexes are located.

Highlights

The positive-sense ribonucleic acid (RNA) viruses of the family Picornaviridae include numerous important human and animal pathogens [1]
In addition to the clear antiviral effects of ARB that suppress the entry of enveloped viruses, fusion [10, 17,18,19,20,21,22, 30], ARB inhibits the infection of cells by non-enveloped picornaviruses, including PV-1 [25] and PV-3 [21] while, as shown in this report, it inhibits foot-and-mouth disease virus (FMDV) replication and equine rhinitis A virus (ERAV) infection
A major question for future work is how ARB blocks FMDV replication and how it prevents the resumption of FMDV replication upon guanidine hydrochloride (GuHCl) removal

Summary

Introduction

The positive-sense RNA viruses of the family Picornaviridae include numerous important human and animal pathogens [1]. Whereas the first three of these species are of little medical or veterinary importance, FMDV is the causative agent of foot-and-mouth disease: a highly contagious, systemic infection of domestic and wild cloven-hooved ruminants [2]. In disease-free countries, outbreaks in the population of domestic livestock result in the culling of millions of animals and significant economic losses. Control of the disease is limited by several factors. These include multiple virus serotypes and subtypes, the difficulty in distinguishing vaccinated from infected animals and an asymptomatic carrier state that some animals can develop [5, 6]

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Results

Conclusion