Enterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. In the recently published study of Jiang et al. (Jilin University, China) show that 2,6-Di-O-methyl-Beta-cyclodextrin (methyl-β-cyclodextrin), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concentrations. The addition of exogenous cholesterol attenuated the anti-EV-D68 activity of 2,6-Di-O-methyl-Beta-cyclodextrin. 2,6-Di-O-methyl-Beta-cyclodextrin treatment had a weak influence on the attachment of viral particles to the cell membrane (RD cells and HeLa cells) but significantly inhibited EV-D68 entry into host cells. It was demonstrated that EV-D68 facilitated the translocation of the viral receptor protein ICAM-5 to membrane rafts in infected cells. The colocalization of viral particles with ICAM-5 in lipid rafts was thoroughly abolished in cells after treatment with 2,6-Di-O-methyl-Beta-cyclodextrin. It was also shown that 2,6-Di-O-methyl-Beta-cyclodextrin inhibited the replication of isolated circulating EV-D68 strains. The anti-EV-D68 activity of 2,6-Di-O-methyl-Beta-cyclodextrin is mainly mediated by modulating host cell resistance to EV-D68 entry but not the direct binding of virions.

In summary, the results demonstrate that 2,6-Di-O-methyl-Beta-cyclodextrin suppresses EV-D68 replication by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts.

2,6-Di-O-methyl-Beta-cyclodextrin