The constrained catalytic activity of conventional nanozymes under neutral pH conditions presents a fundamental challenge that limits their practical applicability in physiological environments. To overcome this limitation, we design a MnO2-supported gold single-atom nanozyme (MnO2-Au SAN) through a freeze-assisted photochemical reduction approach. A key feature of this system is the formation of a strong electronic metal-support interaction (EMSI), which enables efficient electron transfer between atomically dispersed Au sites, the MnO2 substrate, and adsorbed molecular species. By integrating spectroscopic characterization with kinetic measurements, we show that this electron-transfer mechanism significantly enhances oxidase-like activity at neutral pH. The MnO2-Au SAN achieves an exceptionally low Michaelis constant of 0.040 mM for TMB oxidation, superior to that of most reported nanozymes. The catalytic mechanism, investigated through radical scavenging and electron spin resonance analyses, is associated with the enhanced generation of holes and hydroxyl radicals under neutral conditions. When applied to a lateral flow immunoassay for the detection of influenza A virus, the MnO2-Au SAN enables a detection limit of 20 pg/mL using TMB-based signal amplification. This work presents a general EMSI-driven strategy for enhancing nanozyme activity under physiological pH conditions, underscoring the critical importance of atomic-level electron transfer in emulating natural enzymatic reactions.

