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 E. coli 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 E. coli by electron microscopy. Subsequently, the fenobody’s expression level and neutralizing activity were then evaluated.
Results: The results showed that the IC₅₀ of H11-D4 and fenobody Fe-H11-D4 expressed in E. coli were 171.1 nmol L^{− 1} and 20.87 nmol L^{− 1}, respectively. However, the IC₅₀ of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L^{− 1} 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.

Keywords: COVID-19, ferritin, fenobody, baculovirus expression system, silkworm