Key result
SCARB2 mimetic peptide RMP-R8 improves survival and demonstrates potent antiviral activity against enteroviruses.
Why the study?
EV-A71 and CV-A16 cause severe HFMD with high childhood mortality and lack specific antiviral therapies, while extracellular SCARB2-Fc decoys fail to block infection.
Does the cell-penetrating SCARB2 mimetic peptide RMP(R8) improve survival and inhibit viral entry in models of EV-A71 and CV-A16 infection?
Does the cell-penetrating SCARB2 mimetic peptide RMP(R8) improve survival and inhibit viral entry in models of EV-A71 and CV-A16 infection?
Effect estimate: EC50 = 0.156 μg/mL
The engineered cell-penetrating SCARB2 mimetic peptide RMP(R8) successfully blocks viral entry and improves survival in preclinical enterovirus models, offering a generalizable strategy to drug virus-receptor interactions inside cells.
May support intracellular mimetic development for enteroviruses; hypothesis-generating with human efficacy and safety untested.
Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are leading causes of severe hand, foot, and mouth disease (HFMD) with high childhood mortality and no specific antiviral therapy. SCARB2 is the essential uncoating receptor, yet extracellular SCARB2-Fc decoys fail to block infection, representing a decade-old paradox in enterovirus therapeutics. Here, we overcome this limitation by engineering RMP(R8), a cell-penetrating SCARB2 mimetic peptide comprising the minimal VP2-binding domain (W146-K166) fused to an octa-arginine transporter. RMP(R8) shows potent antiviral activity (EC 50 = 0.156 μg/mL), outstanding safety (selectivity index > 2003), and excellent aqueous solubility, a critical asset for clinical translation. It broadly inhibits genetically divergent EV-A71 isolates and CV-A16 in intestinal and neural cells by blocking viral entry. In a lethal neonatal mouse model, RMP(R8) increases survival against EV-A71 and CV-A16 challenge in vivo . Intracellular receptor mimicry thus establishes a generalizable strategy for viruses refractory to extracellular intervention. RMP(R8) is a promising clinical candidate to address the unmet need for targeted anti-enterovirus treatment, and our findings redefine how to drug virus-receptor interactions that act inside cells.
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Wang et al. (2026) studied Enterovirus A71 and coxsackievirus A16 infection (hand, foot, and mouth disease). RMP(R8) (cell-penetrating SCARB2 mimetic peptide) was evaluated on Antiviral activity and survival in a lethal neonatal mouse model (EC50 = 0.156 μg/mL). The cell-penetrating SCARB2 mimetic peptide RMP(R8) demonstrated potent antiviral activity (EC50 = 0.156 μg/mL) and increased survival against EV-A71 and CV-A16 in a neonatal mouse model.
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