PLoS Pathogens (Jul 2022)

The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: The case of the spike A222V mutation.

  • Tiziana Ginex,
  • Clara Marco-Marín,
  • Miłosz Wieczór,
  • Carlos P Mata,
  • James Krieger,
  • Paula Ruiz-Rodriguez,
  • Maria Luisa López-Redondo,
  • Clara Francés-Gómez,
  • Roberto Melero,
  • Carlos Óscar Sánchez-Sorzano,
  • Marta Martínez,
  • Nadine Gougeard,
  • Alicia Forcada-Nadal,
  • Sara Zamora-Caballero,
  • Roberto Gozalbo-Rovira,
  • Carla Sanz-Frasquet,
  • Rocío Arranz,
  • Jeronimo Bravo,
  • Vicente Rubio,
  • Alberto Marina,
  • IBV-Covid19-Pipeline,
  • Ron Geller,
  • Iñaki Comas,
  • Carmen Gil,
  • Mireia Coscolla,
  • Modesto Orozco,
  • José Luis Llácer,
  • Jose-Maria Carazo

DOI
https://doi.org/10.1371/journal.ppat.1010631
Journal volume & issue
Vol. 18, no. 7
p. e1010631

Abstract

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The S:A222V point mutation, within the G clade, was characteristic of the 20E (EU1) SARS-CoV-2 variant identified in Spain in early summer 2020. This mutation has since reappeared in the Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing the impact of this mutation. Our results reveal that S:A222V promotes an increased RBD opening and slightly increases ACE2 binding as compared to the parent S:D614G clade. Finally, S:A222V does not reduce sera neutralization capacity, suggesting it does not affect vaccine effectiveness.