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

J Phys Chem Lett. 2021 Dec 16;12(49):11850-11857. doi: 10.1021/acs.jpclett.1c03380. Epub 2021 Dec 7.

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.

MeSH terms

  • 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
  • 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

Substances

  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • COVID-19 breakthrough infections
  • SARS-CoV-2 variants