Ion transport blockers as antivirals
Category: Current
Published Date
Written by Administrator
We have demonstrated that a number of amiloride derivatives have antiviral activity in tissue culture against viruses belonging to 2 medically important genera of the Picornavirus family: coxsackievirus B3 (CVB3, causes myocarditis) and human rhinovirus 2 (HRV2, a common cold virus). The compounds were more effective against CVB3 than against HRV2. Our data suggested that the antiviral activity against coxsackievirus B3 was due to inhibition of viral RNA replication, with the antiviral target likely to be a viral protein. In the case of HRV2, virus release from infected cells was also inhibited. We have generated amiloride-resistant CVB3 mutants by passaging the virus in the presence of the compound. We are currently sequencing the genomes of the resistant virus isolates to identify mutation(s) causing resistance, and thus identify viral protein(s) targeted by amiloride and its derivatives. Once the protein is identified, the studies will be conducted to elucidate the detailed mechanism of antiviral activity. We have analysed anti-CVB3 activity and cytotoxicity of 29 compounds belonging to a large group of chemicals, acylguanidines, which includes amiloride derivatives. The resulting structure-activity data were used to delineate medicinal chemistry strategy aimed at improving the antiviral activity and cytoxicity of the compounds.
