Recently, the SKLRD, in cooperation with Guangzhou Laboratory, Xiamen Institutes of Respiratory Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, and Huaqiao University, has published a research paper with the title of “A Class of Shark-Derived Single-Domain Antibodies can Broadly Neutralize SARS-Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape” on the journal Small Methods.

As COVID-19 continues to spread around the world, the constant emergence of mutant strains poses great challenges to existing vaccines and therapeutic antibodies, so more prevention and treatments are urgently needed. The development of broad-spectrum neutralizing antibodies is a promising treatment and prevention strategy for the current COVID-19 pandemic of neocoronal pneumonia.. Nanoantibodies have received increasing attention in recent years. Nanoantibodies have many characteristics better than conventional IgG antibodies, such as low molecular weight, stable physical and chemical properties, low production cost, simple structure for easy transformation, thus boasting great application potential in the bio-pharmaceutical field.

The research team blazed a unique way to screen the anti-novel coronavirus specific nanoantibodies- “micro-nano antibodies” after immunizing sharks that are common in coastal China. The molecular weight of shark micro-nano antibodies is 30% less than that of camel source nanoantibodies. The researchers obtained micro-nano antibodies that can effectively neutralize novel coronavirus mutant strains including Wuhan, Alpha, Beta, Kappa, Delta, Lambda, and Pangolin CoV and Bat CoV of the Sarbecovirus family. In a mouse model, shark nanoantibodies can effectively prevent and treat novel coronavirus infection by intranasal administration. Crystal structure analysis revealed that the shark nanoantibodies used the unique “WXGY” gene motif in its CDR3 region to bind to the conserved site of the novel coronavirus RBD domain, so as to enable its broad-spectrum binding capability. This study also clarified that S375F is the main mutational site of shark micro-nano antiboties to be neutralized by Omicron mutants, providing ideas for the study of novel coronavirus escape mechanism and the development of vaccines and antibodies. The team is currently developing a nasal spray based on shark nanoantibodies for prophylactic blockade of novel coronavirus infection.