James H. Naismith

Nanobodies are derived from camelid species and have a single heavy chain. This single heavy chain contains three variable regions that govern antigen recognition. Using two different methods, we have raised nanobodies agains the pandemic SARS-CoV-2 virus. We reported the first full structural characterization of potently neutralizing nanobodies showing that they rely on striking pi-cation interaction. One of our approaches produced a series of nanobodies with increasing binding energy, we have subsequently used this to disentangle the molecular contributions to affinity and with EM data designed more potent agents. At the same time using inoculation of llama’s we identified the most potent neutralizing agent so far described against the virus. The agent was highly effective in animals given topically or by infection. I will report our current efforts to identify agents that are equally effective against the new omicron strains.