Posted by MβCD was found again to have antiviral effect, but in this case the Chinese scientists found that the cholesterol removal from the host cells inhibits not the docking of the virions studied, but their entry into the host cells.
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) [1] show that methyl-β-cyclodextrin (MβCD), 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 MβCD. MβCD 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 MβCD. It was also shown that MβCD inhibited the replication of isolated circulating EV-D68 strains. The anti-EV-D68 activity of MβCD 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 MβCD suppresses EV-D68 replication by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts.
[1] Jiang, Y., Liu, S., Shen, S., Guo, H., Huang, H., Wei, W., Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in
lipid rafts, Antiviral Research (2020), doi: https://doi.org/10.1016/j.antiviral.2020.104752.