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Beautiful study showing the identification of a single domain antibody that binds coronavirus spike protein (raised against SARS-CoV-1, cross-reacts with #SARSCoV2) @CellCellPress @McLellan_Lab 1/6 https://www.cell.com/cell/fulltext/S0092-8674(20)30494-3
Goal was to find antibodies that neutralise MERS-CoV and SARS-CoV-1, both of which use spike protein to enter cells. Authors immunised a llama with spike protein from both viruses (stabilised in the conformation it adopts before it binds to cells). 2/6
The llama developed antibodies against these spike proteins, some of which were the smaller single domain antibodies (nanobodies) typical of camelids. 3/6
The authors were able to identify a nanobody against SARS-CoV-1, and another against MERS-CoV, and each showed neutralising activity against the relevant pseudovirus. They made crystal structures to decipher how binding of the nanobodies impeded virus entry into cells. 4/6
Importantly, the nanobody against SARS-CoV-1 spike could cross-react with #SARSCoV2 spike. A bivalent Fc-fusion version of this nanobody (VHH-72-Fc) could neutralise #SARSCoV2 S pseudotyped viruses. This fusion protein was amenable to large-scale production. 5/6
Antibodies can be used as therapeutics, but are short-lived so don’t replace the need for a vaccine. These smaller camelid antibodies are of interest since they can be nebulized and inhaled into the lungs & are stable to prolonged storage so can potentially be stockpiled. 6/6
