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-Rodríguez; 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

doi:10.1371/journal.ppat.1010631

Molecular BiologyPLoS PathogensJul 11, 2022

Peer-reviewed journal article

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 iD, Clara Marco‐Marín iD, Miłosz Wieczór iD, Carlos P. Mata iD, James Krieger iD, Paula Ruiz-Rodríguez iD, Maria Lopez-Redondo iD, Clara Francés‐Gómez iD, Roberto Melero iD, Carlos Óscar S. Sorzano iD, Marta Martínez iD, Nadine Gougeard iD, Alicia Forcada‐Nadal iD, Sara Zamora‐Caballero iD, Roberto Gozalbo‐Rovira iD, Carla Sanz-Frasquet iD, Rocío Arranz iD, Jerónimo Bravo iD, Vicente Rubio iD, Alberto Marina iD, The IBV-Covid19-Pipeline, Ron Geller iD, Iñaki Comas iD, Carmen Gil iD, Mireia Coscollá iD, , J.M. Carazo iD

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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