PURPOSE: COVID-19 is rampant throughout the world, which has caused great damage to human lives and seriously hindered the development of the global economy. Aiming at the treatment of SARS-CoV-2, in this study, we proposed a novel fenobody strategy based on ferritin (Fe) self-assembly technology. METHODS: The neutralizing nanobody H11-D4 of SARS-CoV-2 fused to the C-terminus of end-modified human ferritin was expressed in and silkworm baculovirus expression systems. A large number of nanoparticles were successfully self-assembled in silkworms, while relatively few nanoparticles can be observed in the treated products from by electron microscopy. Subsequently, the fenobody's expression level and neutralizing activity were then evaluated. RESULTS: The results showed that the IC of H11-D4 and fenobody Fe-H11-D4 expressed in were 171.1 nmol L and 20.87 nmol L, respectively. However, the IC of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L showing better neutralization activity. CONCLUSION: Therefore, fenobodies can be well self-assembled in silkworm baculovirus expression system, and ferritin self-assembly technology can effectively improve nanobody neutralization activity.