Can we replay viral evolution in billions of people in the lab - and even predict where it is heading? We used in vitro protein evolution to explore how the SARS-CoV-2 spike protein evolved during the last 6 years. Under strong selection for ACE2 binding, sequences starting from early SARS-CoV-2 variants rapidly evolved mutations remarkably similar to those later seen in Omicron and its sub-lineages. Weaker selection produced fewer Omicron-like changes, while evolution starting from Omicron preserved its defining mutations independently on the evolutionary pressure. As the receptor binding domain of the spike protein has the highest mutation rate of all SARS-CoV-2 proteins, these results reveal that for SARS-CoV-2 strong receptor binding shapes viral evolution and demonstrate the potential of in vitro evolution to uncover - and potentially anticipate - future evolutionary trajectories.
Prof. Dr. Gideon Schreiber forscht am Weizmann Institute of Science, Israel.
