Mechanisms of SARS-CoV-2 Evolution Revealing Vaccine-Resistant Mutations in Europe and America
- Rui WangRui WangDepartment of Mathematics, Michigan State University, East Lansing, Michigan 48824, United StatesMore by Rui Wang,
- Jiahui ChenJiahui ChenDepartment of Mathematics, Michigan State University, East Lansing, Michigan 48824, United StatesMore by Jiahui Chen, and
- Guo-Wei Wei*Guo-Wei Wei*Email: wei@math.msu.eduDepartment of Mathematics, Michigan State University, East Lansing, Michigan 48824, United StatesDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United StatesDepartment of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824, United StatesMore by Guo-Wei Wei
Abstract
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.
The log 2 enrichment ratio is collected from the experimental deep mutation enrichment data in ref (30).
Cited By
This article is cited by 1 publications.
- Jiahui Chen, Rui Wang, Nancy Benovich Gilby, Guo-Wei Wei. Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance. Journal of Chemical Information and Modeling 2022, 62 (2) , 412-422. https://doi.org/10.1021/acs.jcim.1c01451