The evolution of the mechanisms of SARS-CoV-2 evolution revealing vaccine-resistant mutations in Europe and America

Abstract: The importance of understanding SARS-CoV-2 evolution cannot be overemphasized. Recent studies confirm that natural selection is the dominating mechanism of SARS-CoV-2 evolution, which favors mutations that strengthen viral infectivity. We demonstrate that vaccine-breakthrough or antibody-resistant mutations provide a new mechanism of viral evolution. Specifically, vaccine-resistant mutation Y449S in the spike (S) protein receptor-bonding domain (RBD), which occurred in co-mutation [Y449S, N501Y], has reduced infectivity compared to the original SARS-CoV-2 but can disrupt existing antibodies that neutralize the virus. By tracing the evolutionary trajectories of vaccine-resistant mutations in over 1.9 million SARS-CoV-2 genomes, we reveal that the occurrence and frequency of vaccine-resistant mutations correlate strongly with the vaccination rates in Europe and America. We anticipate that as a complementary transmission pathway, vaccine-resistant mutations will become a dominating mechanism of SARS-CoV-2 evolution when most of the world's population is vaccinated. Our study sheds light on SARS-CoV-2 evolution and transmission and enables the design of the next-generation mutation-proof vaccines and antibody drugs.