Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis

Viruses. 2023 Mar 27;15(4):856. doi: 10.3390/v15040856.

Abstract

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

Keywords: COVID-19; SARS-CoV-2; VoC; evolution; mutations; spike protein.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Mutation
  • Protein Binding
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus* / genetics

Substances

  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Grants and funding

Rajeev Tyagi would like to express his gratitude to DBT, New Delhi, Ramalingaswami Re-entry Fellowship Project (No. BT/RLF/Re-entry/27/2018) and Indian Council of Medical Research (ICMR), and New Delhi extramural grant (35/1/2020-Nano/BMS) for generously supporting this study. Nikunj Tandel would like to thank the Indian Council of Medical Research (ICMR) for providing the fellowship to carry out his research (ICMR award letter No.: 2020-7623/CMB-BMS).