Browsing by Author "Ward, Joseph"
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Item The broad-spectrum antiviral drug arbidol inhibits foot-and-mouth disease virus replication(Microbiology Society, UK, 2012) Polyak, Stephen; Adeyemi, Oluwapelumi; Ward, Joseph; Tuthill, TobiArbidol (arb, umifenovir) is used clinically in several countries as an anti-influenza virus drug. We have previously shown that arb inhibits many viruses including hepatitis C virus, Ebola and Zika, and that the primary mode of action appears to be via inhibition of virus entry and/or fusion of viral membranes with intracellular endosomal membranes. We have also shown that arb is a good inhibitor of (non-enveloped) poliovirus types 1 and 3. Here, we evaluate the antiviral potential of arb against another picornavirus, foot-and-mouth disease virus (FMDV), an important veterinary pathogen. Sub-cytotoxic concentrations of arb inhibited the replication of FMDV replicon RNA. arb inhibition of FMDV RNA replication was not a result of generalised inhibition of uptake of cargo (e.g. plasmid DNA or RNA), nor did arb inhibit FMDV replication when added at 4 h post-transfection of FMDV replicon RNA. FMDV replication was blocked by the replication inhibitor guanidium hydrochloride (GuHCl). Upon GuHCl removal, FMDV replication was restored, and arb suppressed this recovery of virus replication. For other picornaviruses, recovery of virus replication upon GuHCl removal has been shown to require translation. However, arb did not suppress cap- or internal ribosome entry site (IRES)-dependent translation. arb also inhibited infectious equine rhinitis associated virus (ERAV), a close relative of FMDV. Testing of arb against infectious FMDV is in progress. Collectively, the data demonstrate that arb inhibits certain picornaviruses by a mechanism that appears to be independent of effects on virus entry but involves inhibition of genome replication.Item The broad-spectrum antiviral drug arbidol inhibits foot-andmouth disease virus genome replication(Microbiology Society, UK., 2019) Herod, Morgan R; Adeyemi, Oluwapelumi Olufemi; Ward, Joseph; Bentley, Kirsten; Harris, Mark; Stonehouse, Nicola; Polyak, StephenArbidol (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 subgenomic 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 nonenveloped picornaviruses. The data are consistent with inhibition of picornavirus genome replication, possibly via the disruption of intracellular membranes on which replication complexes are located.