A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 Delta spike

We used a new deep mutational scanning platform based on non-replicative pseudotyped lentiviruses to quantify how spike mutations impact antibody neutralization and pseudovirus infection. We demonstrated this new platform by making libraries of the SARS-CoV-2 Delta spike. These libraries each contain ~7000 distinct amino-acid mutations in the context of up to ~135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor binding domain, N-terminal domain, and S2 subunit of spike.