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 Lopez-Redondo, Clara Francés‐Gómez, Roberto Melero, Carlos Óscar S. Sorzano, Marta Martínez, Nadine Gougeard, Alicia Forcada‐Nadal, Sara Zamora‐Caballero, Roberto Gozalbo‐Rovira, Carla Sanz-Frasquet, Rocío Arranz, Jerónimo Bravo, Vicente Rubio, Alberto Marina, The IBV-Covid19-Pipeline, Ron Geller, Iñaki Comas, Carmen Gil, Mireia Coscollá, Modesto Orozco, J.L. Llacer, J.M. Carazo
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 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.