Applications of nanobodies in the prevention, detection, and treatment of the evolving SARS-CoV-2

Global health and economy are deeply influenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its newly emerging variants. Nanobodies with nanometer-scale size are promising for the detection and treatment of SARS-CoV-2 and its variants because they are superior to conventional antibodies in terms of cryptic epitope accessibility, tissue penetration, cost, formatting adaptability, and especially protein stability, which enables their aerosolized specific delivery to lung tissues. This review summarizes the progress in the prevention, detection, and treatment of SARS-CoV-2 using nanobodies, as well as strategies to combat the evolving SARS-CoV-2 variants. Generally, highly efficient generation of potent broad-spectrum nanobodies targeting conserved epitopes or further construction of multivalent formats targeting non-overlapping epitopes can promote neutralizing activity against SARS-CoV-2 variants and suppress immune escape.