Mechanisms of SARS-CoV‑2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America

• Published in: The journal of physical chemistry letters Vol. 12; no. 49; pp. 11850 - 11857
• Main Authors: Wang, Rui, Chen, Jiahui, Wei, Guo-Wei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 16.12.2021
• Subjects: Americas; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - metabolism; Antibodies, Neutralizing - immunology; COVID-19 - diagnosis; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 Vaccines - administration & dosage; Europe; Evolution, Molecular; Humans; Mutation; Physical Insights into Materials and Molecular Properties; Protein Binding; Protein Domains - genetics; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - metabolism; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Vaccination; Americas; Europe
• ISSN: 1948-7185; 1948-7185
• DOI: 10.1021/acs.jpclett.1c03380

The importance of understanding SARS-CoV-2 evolution cannot be overlooked. Recent studies confirm that natural selection is the dominating mechanism of SARS-CoV-2 evolution, which favors mutations that strengthen viral infectivity. Here, 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-binding domain, which occurred in co-mutations Y449S and N501Y, has reduced infectivity compared to that of the original SARS-CoV-2 but can disrupt existing antibodies that neutralize the virus. By tracking the evolutionary trajectories of vaccine-resistant mutations in more than 2.2 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-breakthrough or antibody-resistant mutations, like those in Omicron, will become a dominating mechanism of SARS-CoV-2 evolution when most of the world’s population is either vaccinated or infected. 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.