Combining receptor engineering and intracellular gelation for cell-based antiviral therapy against coxsackievirus B3

Viral myocarditis (VMC), caused by pathogens such as coxsackievirus B3 (CVB3), leads to severe cardiac injury and currently lacks specific therapeutic options. Here, we report a biomimetic antiviral strategy based on receptor engineering and intracellular gelation. By combining genetic and protein engineering, we generated a high-affinity Coxsackievirus and adenovirus receptor mutant (Mut-1_CAR) that markedly enhances the binding of host cardiomyocytes to CVB3. Using photochemical crosslinking, these engineered cells were converted into structurally stable, function-retaining gelated cells (PMs). PMs efficiently adsorb and neutralize virus particles, significantly reducing CVB3 plaque formation in vitro. In a murine model of viral myocarditis, PMs demonstrated excellent in vivo safety and biocompatibility while effectively lowering viral load and mitigating myocardial injury. This study establishes a "receptor enhancement + function fixation" approach for non-immune-dependent viral neutralization, providing a conceptual and technical foundation for the development of novel cell-based biomimetic antiviral therapies.