Rapid Discovery of Potent Neutralizing Antibodies against SARS-CoV-2 through Directed Evolution of SARS-CoV-1 Antibodies

The emergence of SARS-CoV-1 in 2002 and SARS-CoV-2 in 2019, alongside evolving viral variants, underscores the ongoing threat posed by novel coronaviruses. Monoclonal antibodies have proven effective against these viruses, but most are derived from convalescent patients' B cells, which represent a limited resource during the early stages of an outbreak. This highlights the need for a robust platform to swiftly discover potent virus-neutralizing antibodies. We propose a strategy to leverage pre-existing neutralizing antibodies targeting viruses that utilize the same receptor entry mechanism. Although three anti-SARS-CoV-1 antibodies (80R, m396, and S230) did not bind to the SARS-CoV-2 RBD, we employed bacterial display-based high-throughput directed evolution and successfully isolated two antibodies, IJ4G and IJ225, which exhibited a strong binding affinity to both SARS-CoV-2 wild-type an…