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

  1. Tiziana Ginex
  2. Clara Marco-MarĂ­n
  3. Miłosz Wieczór
  4. Carlos P. Mata
  5. James Krieger
  6. Maria Luisa LĂłpez-Redondo
  7. Clara Francés-Gómez
  8. Paula Ruiz-Rodriguez
  9. Roberto Melero
  10. Carlos Óscar Sánchez-Sorzano
  11. Marta MartĂ­nez
  12. Nadine Gougeard
  13. Alicia Forcada-Nadal
  14. Sara Zamora-Caballero
  15. Roberto Gozalbo-Rovira
  16. Carla Sanz-Frasquet
  17. Jeronimo Bravo
  18. Vicente Rubio
  19. Alberto Marina
  20. The IBV-Covid19-Pipeline
  21. Ron Geller
  22. Iñaki Comas
  23. Carmen Gil
  24. Mireia Coscolla
  25. Modesto Orozco
  26. José Luis Llácer
  27. José-Maria Carazo
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Abstract

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 now 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.

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