The adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus

Abstract

Bananins are a class of antiviral compounds with a unique structural signature incorporating a trioxa-adamantane moiety covalently bound to a pyridoxal derivative. Six members of this class of compounds: bananin, iodobananin, vanillinbananin, ansabananin, eubananin, and adeninobananin were synthesized and tested as inhibitors of the SARS Coronavirus (SCV) helicase. Bananin, iodobananin, vanillinbananin, and eubananin were effective inhibitors of the ATPase activity of the SCV helicase with IC 50 values in the range 0.5-3 μM. A similar trend, though at slightly higher inhibitor concentrations, was observed for inhibition of the helicase activities, using a FRET-based fluorescent assay. In a cell culture system of SCV, bananin exhibited an EC 50 of less than 10 μM and a CC 50 of over 300 μM. Kinetics of inhibition are consistent with bananin inhibiting an intracellular process or processes involved in SCV replication. © 2005 Elsevier Ltd All rights reserved.