Structural Biology of Nanobodies against the Spike Protein of SARS-CoV-2

Nanobodies are 130 amino acid single-domain antibodies (VHH) derived from the unique heavy-chain-only subclass of Camelid immunogloblins. Their small molecular size, facile expression, high affinity and stability have combined to make them unique targeting reagents with numerous applications in the biomedical sciences. The first nanobody agent has now entered the clinic as a treatment against a blood disorder. The spread of the SARS-CoV-2 virus has seen the global scientific endeavour work to accelerate the development of technologies to try to defeat a pandemic that has now killed over four million people. In a remarkably short period of time, multiple studies have reported nanobodies directed against the viral Spike protein. Several agents have been tested in culture and demonstrate potent neutralisation of the virus or pseudovirus. A few agents have completed animal trials with very encouraging results showing their potential for treating infection. Here, we discuss the structural features that guide the nanobody recognition of the receptor binding domain of the Spike protein of SARS-CoV-2.

Automated summary

Nanobodies, derived from heavy-chain-only subclass of Camelid immunogloblins, are small-sized molecules with high affinity and stability, making them unique targeting reagents in biomedical sciences. With the rapid spread of SARS-CoV-2, nanobodies directed against the viral Spike protein have shown promising results in neutralizing the virus, with some agents already undergoing clinical trials. Researchers are studying the structural features guiding nanobody recognition to develop effective treatments against the pandemic.