1. The structural role of SARS-CoV-2 genetic background in the emergence and success of spike mutations: the case of the spike A222V mutation
- Author
-
Ginex, Tiziana, Marco-Marín, Clara, Wieczór, Miłosz, Mata, Carlos P., Krieger, James, López-Redondo, Maria Luisa, Francés-Gómez, Clara, Ruiz-Rodriguez, Paula, Melero, Roberto, Sánchez-Sorzano, Carlos Óscar, Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Bravo, Jeronimo, Rubio, Vicente, Marina, Alberto, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscolla, Mireia, Orozco, Modesto, Llácer, José Luis, Carazo, José-Maria, European Commission, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Comunidad de Madrid, European Research Council, Instituto de Salud Carlos III, Banco Santander, Generalitat Valenciana, Ginex, Tiziana [0000-0002-5739-8713], Marco-Marín, Clara [0000-0002-8813-3515], Wieczor, Milosz [0000-0003-4990-8629], Mata, Carlos P. [0000-0003-3381-7431], Krieger, James [0000-0001-6194-6244], López-Redondo, Marisa [0000-0002-3328-6821], Francés-Gómez, Clara [0000-0001-7341-3824], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Melero, Roberto [0000-0001-9467-9381], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], Martínez, Marta [0000-0002-8435-5540], Gougeard, Nadine [0000-0001-7338-7267], Forcada-Nadal, Alicia [0000-0003-0179-4044], Zamora-Caballero, Sara [0000-0003-4717-8845], Gozalbo-Rovira, Roberto [0000-0003-3427-3800], Sanz-Frasquet, Carla [0000-0002-6990-3131], Bravo, Jerónimo [0000-0001-6695-2846], Rubio, Vicente [0000-0001-8124-1196], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], Comas, Iñaki [0000-0001-5504-9408], Gil, Carmen [0000-0002-3882-6081], Coscollá, Mireia [0000-0003-0752-0538], Orozco, Modesto [0000-0002-8608-3278], Llácer, José Luis [0000-0001-5304-1795], Carazo, José M. [0000-0003-0788-8447], Ginex, Tiziana, Marco-Marín, Clara, Wieczor, Milosz, Mata, Carlos P., Krieger, James, López-Redondo, Marisa, Francés-Gómez, Clara, Ruiz-Rodríguez, Paula, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, and Carazo, José M.
- Subjects
0303 health sciences ,03 medical and health sciences ,010402 general chemistry ,01 natural sciences ,3. Good health ,030304 developmental biology ,0104 chemical sciences - 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., This research work was supported by the European Commission–NextGenerationEU through the CSIC Global Health Platform. Additionally, authors would like to acknowledge economic support from the Spanish Ministry of Science and Innovation through Grants: PID2019-104757RB-I00 funded by MCIN/AEI/ 10.13039/501100011033, RTI2018-094399-A-I00, and “ERDF A way of making Europe”, by the “European Union”, Grant SEV 2017-0712 funded by MCIN/AEI /10.13039/501100011033, the “Comunidad Autónoma de Madrid" through Grant: S2017/BMD3817, and the European Union (EU) and Horizon 2020 through grants: Marie-Curie Fellowship EnLaCES (MSCA IF 2020, Proposal: 101024130) (to JK), HighResCells (ERC - 2018 - SyG, Proposal: 810057), and iNEXT-Discovery (Proposal: 871037). AM, VR, JB and JLL are funded by CIBERER-ISCIII (proposal: COV20/00437), Fondo Supera COVID-19 (proposal: CSICCOVID19-082), Banco Santander (Proposal: BlockAce), and CSIC PTI Salud Global (Proposal: 202080E110). VR is funded by the Spanish Ministry of Science and Innovation through Grant PID2020-120322RB-C21. IC is funded by project PID2019-104477RB-100, Fondo COVID COV20/00140 and ERC CoG 101001038. MC is funded by the RyC program from the Spanish Ministry of Science and Innovation, the Generalitat Valenciana (SEJI/2019/011).
- Full Text
- View/download PDF