Intracellular SCARB2 mimicry overcomes decoy failure to broadly inhibit enteroviruses.

Intracellular SCARB2 mimicry with RMP(R8) broadly inhibits enteroviruses, overcoming extracellular decoy failure with potent antiviral activity and high safety in vitro and in vivo.

• Why it matters: Enterovirus A71 and coxsackievirus A16 cause severe hand, foot, and mouth disease with high childhood mortality, yet lack specific antiviral therapies, partly due to the failure of extracellular SCARB2-Fc decoys to block infection.
• What they did: Researchers engineered RMP(R8), a cell-penetrating SCARB2 mimetic peptide targeting the VP2-binding domain, and tested its antiviral effects across diverse viral isolates and cell types, including in a neonatal mouse model.
• The result: RMP(R8) demonstrated an EC50 of 0.156 μg/mL, a selectivity index over 2003, and increased survival in infected neonatal mice, establishing intracellular receptor mimicry as a promising strategy for broad anti-enterovirus therapy.