Antiviral activity against enterovirus 71 of sulfated rhamnan isolated from the green alga Monostroma latissimum

Polysaccharide from Monostroma latissimum PML is a sulfated rhamnan, which consists of -> 3)-alpha-L-Rhap-(1 -> and -> 2)-alpha-L-Rhap-(1 -> residues with partial branches and sulfate groups at C-2 of -> 3)-alpha-L-Rhap-(1 -> and/or C-3 of -> 2)-alpha-L-Rhap-(1 ->. The anti-enterovirus 71 (EV71) activity in vitro of PML was assessed by cytopathic effect inhibition and plaque reduction assays, and the results showed that PML was non-cytotoxic and significantly inhibited EV71 infection. The mechanism analysis of anti-EV71 activity demonstrated that PML largely inhibited viral replication before or during viral adsorption, mainly by targeting the capsid protein VP1. PML may also inhibit some early steps of infection after viral adsorption by modulating signaling through the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway. Moreover, PML markedly improved survival and decreased viral titers in EV71-infected mice. The investigation revealed that PML has potential as a novel anti-EV71 agent targeting the viral capsid protein as well as cellular EGFR/PI3K/Akt pathway.