Group B Coxsackieviruses (CVB) are non-enveloped small RNA viruses in the genus Enterovirus, family Picornaviridae. CVB
infection causes diverse conditions from
common cold to
myocarditis,
encephalitis, and
pancreatitis. No specific
antiviral is available for the treatment of CVB
infection.
Anisomycin, a
pyrrolidine-containing
antibiotic and translation inhibitor, was reported to inhibit the replication of some picornaviruses. However, it is unknown if
anisomycin can act as an
antiviral against CVB
infection. Here we observed that
anisomycin showed potent inhibition on CVB type 3 (CVB3)
infection with negligible cytotoxicity when applied at the early stage of
virus infection. Mice infected with CVB3 showed markedly alleviated
myocarditis with reduced viral replication. We found that CVB3
infection significantly increased the transcription of eukaryotic translation
elongation factor 1 alpha 1 (eEF1A1). CVB3 replication was suppressed by EEF1A1 knockdown, while elevated by EEF1A1 overexpression. Similar to the effect of CVB3
infection, EEF1A1 transcription was increased in response to
anisomycin treatment. However, eEF1A1
protein level was decreased with
anisomycin treatment in a dose-dependent manner in CVB3-infected cells. Moreover,
anisomycin promoted eEF1A1 degradation, which was inhibited by the treatment of
chloroquine but not
MG132. We demonstrated that eEF1A1 interacted with the heat shock cognate
protein 70 (HSP70), and eEF1A1 degradation was inhibited by LAMP2A knockdown, implicating that eEF1A1 is degraded through chaperone-mediated autophagy. Taken together, we demonstrated that
anisomycin, which inhibits CVB replication through promoting the lysosomal degradation of eEF1A1, could be a potential
antiviral candidate for the treatment of CVB
infection.