Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Abstract SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion 1 and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry 2,3 . Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus. Here we use pseudovirus deep mutational scanning 4 to measure how more than 9,000 mutations across the full XBB.1.5 and BA.2 spikes affect ACE2 binding, cell entry or escape from human sera. We find that mutations outside the receptor-binding domain (RBD) have meaningfully affected ACE2 binding during SARS-CoV-2 evolution. We also measure how mutations to the XBB.1.5…