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2. Cubierta

Author

Ruiz Rodríguez, Paula A. and Cayuela Sánchez, Salvador

Published
2023

16. ÍNDICE

Author

Ruiz Rodríguez, Paula A. and Cayuela Sánchez, Salvador

Published
2023

18. Frontasunto

Author

Ruiz Rodríguez, Paula A. and Cayuela Sánchez, Salvador

Published
2023

20. VIPERA: Viral Intra-Patient Evolution Reporting and Analysis

Author

Ministerio de Ciencia e Innovación (España), European Research Council, Generalitat Valenciana, Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Sevilla, Jordi [0009-0001-3352-1537], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Vergara, Andrea [0000-0002-5046-4490], Vila, Jordi [0000-0002-8025-3926], Cano-Jiménez, Pablo [0009-0007-4773-3198], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Coscollá, Mireia [0000-0003-0752-0538], Álvarez-Herrera, Miguel, Sevilla, Jordi, Ruiz-Rodríguez, Paula, Vergara, Andrea, Vila, Jordi, Cano-Jiménez, Pablo, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Ministerio de Ciencia e Innovación (España), European Research Council, Generalitat Valenciana, Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Consejo Superior de Investigaciones Científicas (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Sevilla, Jordi [0009-0001-3352-1537], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Vergara, Andrea [0000-0002-5046-4490], Vila, Jordi [0000-0002-8025-3926], Cano-Jiménez, Pablo [0009-0007-4773-3198], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Coscollá, Mireia [0000-0003-0752-0538], Álvarez-Herrera, Miguel, Sevilla, Jordi, Ruiz-Rodríguez, Paula, Vergara, Andrea, Vila, Jordi, Cano-Jiménez, Pablo, González-Candelas, Fernando, Comas, Iñaki, and Coscollá, Mireia

Abstract

Viral mutations within patients nurture the adaptive potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during chronic infections, which are a potential source of variants of concern. However, there is no integrated framework for the evolutionary analysis of intra-patient SARS-CoV-2 serial samples. Herein, we describe Viral Intra-Patient Evolution Reporting and Analysis (VIPERA), a new software that integrates the evaluation of the intra-patient ancestry of SARS-CoV-2 sequences with the analysis of evolutionary trajectories of serial sequences from the same viral infection. We have validated it using positive and negative control datasets and have successfully applied it to a new case, which revealed population dynamics and evidence of adaptive evolution. VIPERA is available under a free software license at https://github.com/PathoGenOmics-Lab/VIPERA.

Published
2024

21. VIPERA: Viral Intra-Patient Evolution Reporting and Analysis

Author

European Commission, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Generalitat Valenciana, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía, Industria y Competitividad (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Sevilla, Jordi [0009-0001-3352-1537], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Vergara, Andrea [0000-0002-5046-4490], Vila, Jordi [0000-0002-8025-3926], Cano-Jiménez, Pablo [0009-0007-4773-3198], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Coscollá, Mireia [0000-0003-0752-0538], Álvarez-Herrera, Miguel, Sevilla, Jordi, Ruiz-Rodríguez, Paula, Vergara, Andrea, Vila, Jordi, Cano-Jiménez, Pablo, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, European Commission, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Generalitat Valenciana, European Research Council, Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Economía, Industria y Competitividad (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Sevilla, Jordi [0009-0001-3352-1537], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Vergara, Andrea [0000-0002-5046-4490], Vila, Jordi [0000-0002-8025-3926], Cano-Jiménez, Pablo [0009-0007-4773-3198], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Coscollá, Mireia [0000-0003-0752-0538], Álvarez-Herrera, Miguel, Sevilla, Jordi, Ruiz-Rodríguez, Paula, Vergara, Andrea, Vila, Jordi, Cano-Jiménez, Pablo, González-Candelas, Fernando, Comas, Iñaki, and Coscollá, Mireia

Abstract

Viral mutations within patients nurture the adaptive potential of SARS-CoV-2 during chronic infections, which are a potential source of variants of concern. However, there is no integrated framework for the evolutionary analysis of intra-patient SARS-CoV-2 serial samples. Herein we describe VIPERA (Viral Intra-Patient Evolution Reporting and Analysis), a new software that integrates the evaluation of the intra-patient ancestry of SARS-CoV-2 sequences with the analysis of evolutionary trajectories of serial sequences from the same viral infection. It has been validated using positive and negative control datasets and successfully applied to a novel case, contributing to easy and automatic analysis of intra-patient SARS-CoV-2 sequences.

Published
2023

22. Bioinformatics analysis of mutations in SARSCoV- 2 and clinical phenotypes

Author

European Commission, Consejo Superior de Investigaciones Científicas (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Navarro-Domínguez, Beatriz [0000-0003-4077-8696], Rodríguez Santana, Simón [0000-0003-3760-0520], García Rasines, Daniel [0000-0002-1558-5860], Naveiro Flores, Roi [0000-0001-9032-2465], Gil, Carmen [0000-0002-3882-6081], Carazo, José M. [0000-0003-0788-8447], Coscollá, Mireia [0000-0003-0752-0538], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], Campillo, Nuria E. [0000-0002-9948-2665], Ulzurrun, Eugenia, Del Hoyo, Daniel, Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Rodríguez Santana, Simón, García Rasines, Daniel, Naveiro Flores, Roi, Gil, Carmen, Carazo, José M., Coscollá, Mireia, Sorzano, Carlos Óscar S., Campillo, Nuria E., European Commission, Consejo Superior de Investigaciones Científicas (España), Álvarez-Herrera, Miguel [0000-0002-7922-3180], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Navarro-Domínguez, Beatriz [0000-0003-4077-8696], Rodríguez Santana, Simón [0000-0003-3760-0520], García Rasines, Daniel [0000-0002-1558-5860], Naveiro Flores, Roi [0000-0001-9032-2465], Gil, Carmen [0000-0002-3882-6081], Carazo, José M. [0000-0003-0788-8447], Coscollá, Mireia [0000-0003-0752-0538], Sorzano, Carlos Óscar S. [0000-0002-9473-283X], Campillo, Nuria E. [0000-0002-9948-2665], Ulzurrun, Eugenia, Del Hoyo, Daniel, Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Rodríguez Santana, Simón, García Rasines, Daniel, Naveiro Flores, Roi, Gil, Carmen, Carazo, José M., Coscollá, Mireia, Sorzano, Carlos Óscar S., and Campillo, Nuria E.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially reported in Wuhan (China) hasspread worldwide. Like other viruses, SARS-CoV-2 accumulates mutations with each cycle of replication by continuously evolving a viral strain with one or more single nucleotide variants (SNVs). However, SNVs that cause severe COVID-19 or lead to immune escape or vaccine failure are not well understood. We aim to identify SNVs associated with severe clinical phenotypes., Methods: In this study, 27429 whole-genome aligned consensus sequences of SARS-CoV-2 were collected from genomic epidemiology of SARS-CoV-2 project in Spain (SeqCOVID) [1]. These samples were obtained from patients who required hospitalization and/or intensive care unit admission (ICU), excluding those registered in the first pandemic wave.Besides, 248 SARS-CoV-2 genomes were isolated from COVID-19 hospitalized patients from Gregorio Marañon General University Hospital (GMH) of which 142 were fully vaccinated. Bioinformatics tools using R and Python programming languages were developed and implemented comparing those to SARS-CoV-2 Wuhan-Hu-1 (reference genome)., Results: Using a selection threshold mutational frequency 10%, 27 SNVs were expected to have association with hospitalization and ICU risk. The reference haplotype differing at the SNV coding for lysine at the residue 203 (N:R203K) was found to have negative association with COVID-19 hospitalization risk (p = 5.37 x 10-04). Similarly, a negative association was observed when the residue at 501 is replaced by tyrosine (S:N501Y) (p = 1.33 x 10-02). The application of a Chi-square test suggested that SNV-haplotypes coding for mutants residues such as (S:A222V, N:A220V, ORF10:V30L) and (ORF1a:T1001I, ORF1a:I2230T, S:N501Y, S:T716S, S:S982A, ORF8:Q27*, N:R203K, N:S235F) have negative associations with COVID-19 hospitalization risk (p = 6.58 x 10-07 and p = 2.27 x 10-16, respectively) and COVID-19 ICU risk (p = 1.15 x 10-02 and p = 2.51 x 10-02, respectively). Focusing on the SNV-haplotype coding the mutations (S:A222V, N:A220V, N:D377Y, ORF10:V30L) were observed to increase the risk of COVID-19 hospitalization (p = 2.71 x 10-04). Results from SARS-CoV-2 genomes analysis from GMH showed 63 coding SNVs which met the established threshold value. Applying a Chi-square test, the SNV-haplotype carrying coding variants for mutant residues in 5 ORF proteins and surface and membrane glycoprotein and nucleocapsid phosphoprotein was significantly associated with vaccine failure in hospitalized COVID-19 patients (p = 7.91 x 10-04)., Conclusions: SNV-haplotypes carrying variants lead to non-synonymous mutations located along SARS-CoV-2 wholeproteome may influence COVID-19 severity and vaccine failure suggesting a functional role in the clinical outcome for COVID-19 patients.

Published
2022

23. 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

European Commission, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Generalitat Valenciana, Comunidad de Madrid, Banco Santander, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), 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], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], López-Redondo, Marisa [0000-0002-3328-6821], Francés-Gómez, Clara [0000-0001-7341-3824], 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], Arranz, Rocío [0000-0001-5321-0915], 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, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, Carazo, José M., European Commission, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia e Innovación (España), Generalitat Valenciana, Comunidad de Madrid, Banco Santander, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), 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], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], López-Redondo, Marisa [0000-0002-3328-6821], Francés-Gómez, Clara [0000-0001-7341-3824], 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], Arranz, Rocío [0000-0001-5321-0915], 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, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, and Carazo, José M.

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.

Published
2022

24. Combinatorial analysis of deletion repair in SARS-CoV-2 variants of concern

Author

Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Zulaica, Joao, Grau, Brayan, Bracho, María Alma, Guerreiro, Manuel, Aguilar-Gallardo, Cristóbal, González-Candelas, Fernando, Comas, Iñaki, Geller, Ron, Coscollá, Mireia, Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Zulaica, Joao, Grau, Brayan, Bracho, María Alma, Guerreiro, Manuel, Aguilar-Gallardo, Cristóbal, González-Candelas, Fernando, Comas, Iñaki, Geller, Ron, and Coscollá, Mireia

Abstract

[Background] The spike protein of SARS-CoV-2 is a key determinant of viral fitness and immune evasion, and its N-terminal domain (NTD) is prone to mutations that may confer fitness advantages to the virus. Most variants of concern (VOCs), including Alpha, Delta, and Omicron, have harbored distinct NTD lineage-defining mutations. However, the relationship between genotype and the impact on viral transmission and viral phenotype is not yet fully understood., [Methods] We analyzed over 10 million SARS-CoV-2 genomes from GISAID to investigate the prevalence and estimate the transmission of different combinations of NTD mutations across the Alpha and the Omicron variants. Additionally, we characterized the viral phenotype of deletion repair events in a surrogate in vitro system, assessing their infectivity, fusogenicity, thermal stability, protein surface expression, and neutralization sensitivity., [Results] Some NTD mutations, such the repair of deleted amino acids at sites S:69/70 and S:144 in Alpha viruses, were associated with an increased transmission rate and higher frequency among older age groups. These deletion repairs were also detected in Omicron, but with different patterns and effects. For instance, the repair of deletion at site S:143/145 in Omicron enhanced viral fusogenicity and neutralization by sera from vaccinated individuals. However, the repair of the deletion at site S:69/70 reduced viral infectivity and did not affect these traits. The co-occurrence of both repairs resulted in reduced fusogenicity., [Conclusions] Our study reveals the complex interplay between NTD mutations, including those that lead to deletion repair, and viral success in SARS-CoV-2. This may have implications for viral transmission, immunity, and vaccine efficacy. Our findings improve our understanding of SARS- CoV-2 evolution, and provide insights for future research and public health interventions.

Published
2023

25. Genomic analysis of Mycobacterium brumae sustains its nonpathogenic and immunogenic phenotype

Author

Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Generalitat de Catalunya, Generalitat Valenciana, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], Renau-Mínguez, Chantal, Herrero-Abadía, Paula, Ruiz-Rodríguez, Paula, Sentandreu, Vicente, Torrents, Eduard, Chiner-Oms, Álvaro, Torres-Puente, Manuela, Comas, Iñaki, Julián, Esther, Coscollá, Mireia, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Generalitat de Catalunya, Generalitat Valenciana, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], Renau-Mínguez, Chantal, Herrero-Abadía, Paula, Ruiz-Rodríguez, Paula, Sentandreu, Vicente, Torrents, Eduard, Chiner-Oms, Álvaro, Torres-Puente, Manuela, Comas, Iñaki, Julián, Esther, and Coscollá, Mireia

Abstract

Mycobacterium brumae is a rapid-growing, non-pathogenic Mycobacterium species, originally isolated from environmental and human samples in Barcelona, Spain. Mycobacterium brumae is not pathogenic and it's in vitro phenotype and immunogenic properties have been well characterized. However, the knowledge of its underlying genetic composition is still incomplete. In this study, we first describe the 4 Mb genome of the M. brumae type strain ATCC 51384T assembling PacBio reads, and second, we assess the low intraspecies variability by comparing the type strain with Illumina reads from three additional strains. Mycobacterium brumae genome is composed of a circular chromosome with a high GC content of 69.2% and containing 3,791 CDSs, 97 pseudogenes, one prophage and no CRISPR loci. Mycobacterium brumae has shown no pathogenic potential in in vivo experiments, and our genomic analysis confirms its phylogenetic position with other non-pathogenic and rapid growing mycobacteria. Accordingly, we determined the absence of virulence-related genes, such as ESX-1 locus and most PE/PPE genes, among others. Although the immunogenic potential of M. brumae was proved to be as high as Mycobacterium bovis BCG, the only mycobacteria licensed to treat cancer, the genomic content of M. tuberculosis T cell and B cell antigens in M. brumae genome is considerably lower than those antigens present in M. bovis BCG genome. Overall, this work provides relevant genomic data on one of the species of the mycobacterial genus with high therapeutic potential.

Published
2023

26. Bioinformatics analysis of mutations in SARSCoV- 2 and clinical phenotypes

Author

Ulzurrun, Eugenia, Del Hoyo, Daniel, Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Rodríguez Santana, Simón, García Rasines, Daniel, Naveiro Flores, Roi, Gil, Carmen, Carazo, José M., Coscollá, Mireia, Sorzano, Carlos Óscar S., Campillo, Nuria E., European Commission, Consejo Superior de Investigaciones Científicas (España), Álvarez-Herrera, Miguel, Ruiz-Rodríguez, Paula, Navarro-Domínguez, Beatriz, Rodríguez Santana, Simón, García Rasines, Daniel, Naveiro Flores, Roi, Gil, Carmen, Carazo, José M., Coscollá, Mireia, Sorzano, Carlos Óscar S., and Campillo, Nuria E.

Abstract

1 p.-1 fig.-8 tab., Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially reported in Wuhan (China) hasspread worldwide. Like other viruses, SARS-CoV-2 accumulates mutations with each cycle of replication by continuously evolving a viral strain with one or more single nucleotide variants (SNVs). However, SNVs that cause severe COVID-19 or lead to immune escape or vaccine failure are not well understood. We aim to identify SNVs associated with severe clinical phenotypes., Methods: In this study, 27429 whole-genome aligned consensus sequences of SARS-CoV-2 were collected from genomic epidemiology of SARS-CoV-2 project in Spain (SeqCOVID) [1]. These samples were obtained from patients who required hospitalization and/or intensive care unit admission (ICU), excluding those registered in the first pandemic wave.Besides, 248 SARS-CoV-2 genomes were isolated from COVID-19 hospitalized patients from Gregorio Marañon General University Hospital (GMH) of which 142 were fully vaccinated. Bioinformatics tools using R and Python programming languages were developed and implemented comparing those to SARS-CoV-2 Wuhan-Hu-1 (reference genome)., Results: Using a selection threshold mutational frequency 10%, 27 SNVs were expected to have association with hospitalization and ICU risk. The reference haplotype differing at the SNV coding for lysine at the residue 203 (N:R203K) was found to have negative association with COVID-19 hospitalization risk (p = 5.37 x 10-04). Similarly, a negative association was observed when the residue at 501 is replaced by tyrosine (S:N501Y) (p = 1.33 x 10-02). The application of a Chi-square test suggested that SNV-haplotypes coding for mutants residues such as (S:A222V, N:A220V, ORF10:V30L) and (ORF1a:T1001I, ORF1a:I2230T, S:N501Y, S:T716S, S:S982A, ORF8:Q27*, N:R203K, N:S235F) have negative associations with COVID-19 hospitalization risk (p = 6.58 x 10-07 and p = 2.27 x 10-16, respectively) and COVID-19 ICU risk (p = 1.15 x 10-02 and p = 2.51 x 10-02, respectively). Focusing on the SNV-haplotype coding the mutations (S:A222V, N:A220V, N:D377Y, ORF10:V30L) were observed to increase the risk of COVID-19 hospitalization (p = 2.71 x 10-04). Results from SARS-CoV-2 genomes analysis from GMH showed 63 coding SNVs which met the established threshold value. Applying a Chi-square test, the SNV-haplotype carrying coding variants for mutant residues in 5 ORF proteins and surface and membrane glycoprotein and nucleocapsid phosphoprotein was significantly associated with vaccine failure in hospitalized COVID-19 patients (p = 7.91 x 10-04)., Conclusions: SNV-haplotypes carrying variants lead to non-synonymous mutations located along SARS-CoV-2 wholeproteome may influence COVID-19 severity and vaccine failure suggesting a functional role in the clinical outcome for COVID-19 patients., This research work was funded by the European Commission-NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global)

Published
2022

27. Evolutionary and phenotypic characterization of spike mutations in a new SARS-CoV-2 Lineage reveals two Variants of Interest

Author

Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula, Frances-Gomez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’Auria, Giuseppe, Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscolla, Mireia, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], and Coscolla, Mireia [0000-0003-0752-0538]

Subjects
2019-20 coronavirus outbreak, Lineage (genetic), Geography, Research council, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), European Regional Development Fund, media_common.cataloged_instance, Spike (database), European union, Valencian community, Genealogy, media_common
Abstract

Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acquired two additional changes previously associated with antibody escape and it could be identified as VOI1163.7.V2. Overall, we have detected the spread of a new Spike variant that may be advantageous to the virus and whose continuous transmission poses risks by the acquisition of additional mutations that could affect pre-existing immunity., This work was funded by the Instituto de Salud Carlos III project COV20/00140 and COV20/00437, Spanish National Research Council project CSIC-COV19-021 and CSIC-COVID19-082, and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI). Action co-financed by the European Union through the Operational Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020. M.C. and R.G. are supported by Ramon y Cajal program from Ministerio de Ciencia.

Published
2021
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28. Evolutionary and phenotypic characterization of spike mutations in a new SARS-CoV-2 Lineage reveals two Variants of Interest

Author

Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], Coscolla, Mireia [0000-0003-0752-0538], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, European Commission, Ruiz-Rodríguez, Paula [0000-0003-0727-5974], Frances-Gomez, Clara [0000-0001-7341-3824], Chiner-Oms, Álvaro [0000-0002-0463-0101], López, Mariana G. [0000-0002-2216-9232], Jiménez Serrano, Santiago [0000-0003-2917-6053], Cancino-Muñoz, Irving [0000-0002-5261-1634], Ruiz-Hueso, Paula [0000-0003-0217-471X], Torres-Puente, Manuela [0000-0002-8352-180X], D’Auria, Giuseppe [0000-0003-0672-2541], Martínez-Priego, Llucia [0000-0002-1073-269X], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Marina, Alberto [0000-0002-1334-5273], Geller, Ron [0000-0002-7612-4611], Coscolla, Mireia [0000-0003-0752-0538], Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, López, Mariana G., Jiménez-Serrano, Santiago, Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, Bracho, María Alma, D’Auria, Giuseppe, Martínez-Priego, Llucia, Guerreiro, Manuel, Montero-Alonso, Marta, Gómez, María Dolores, Piñana, José Luis, Seqcovid-Spain Consortium, González-Candelas, Fernando, Comas, Iñaki, Marina, Alberto, Geller, Ron, and Coscollá, Mireia

Abstract

Molecular epidemiology of SARS-CoV-2 aims to monitor the appearance of new variants with the potential to change the virulence or transmissibility of the virus. During the first year of SARS-CoV-2 evolution, numerous variants with possible public health impact have emerged. We have detected two mutations in the Spike protein at amino acid positions 1163 and 1167 that have appeared independently multiple times in different genetic backgrounds, indicating they may increase viral fitness. Interestingly, the majority of these sequences appear in transmission clusters, with the genotype encoding mutations at both positions increasing in frequency more than single-site mutants. This genetic outcome that we denote as Lineage B.1.177.637, belongs to clade 20E and includes 12 additional single nucleotide polymorphisms but no deletions with respect to the reference genome (first sequence in Wuhan). B.1.177.637 appeared after the first wave of the epidemic in Spain, and subsequently spread to eight additional countries, increasing in frequency among sequences in public databases. Positions 1163 and 1167 of the Spike protein are situated in the HR2 domain, which is implicated in the fusion of the host and viral membranes. To better understand the effect of these mutations on the virus, we examined whether B.1.177.637 altered infectivity, thermal stability, or antibody sensitivity. Unexpectedly, we observed reduced infectivity of this variant relative to the ancestral 20E variant in vitro while the levels of viral RNA in nasopharyngeal swabs did not vary significantly. In addition, we found the mutations do not impact thermal stability or antibody susceptibility in vaccinated individuals but display a moderate reduction in sensitivity to neutralization by convalescent sera from early stages of the pandemic. Altogether, this lineage could be considered a Variant of Interest (VOI), we denote VOI1163.7. Finally, we detected a sub-cluster of sequences within VOI1163.7 that have acqu

Published
2021

29. 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

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, Carazo, José M., 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.

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.

Published
2021

30. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Author

Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D'Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Álex, Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Seqcovid-Spain Consortium, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D'Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, José Antonio, Bordoy, Antoni E., Canut, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, María Luz, Costa-Alcalde, José J., Toro, María de, Toro Peinado, Inmaculada de, Pozo, José Luis del, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno, Concepción, González Galán, Verónica, Gonzalo Jimeno, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José A., López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, María Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Álex, Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Seqcovid-Spain Consortium, Coscollá, Mireia, González-Candelas, Fernando, and Comas, Iñaki

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re < 1), also reflected in the replacement of SECs by a new variant over the summer of 2020. In summary, we reveal a notable difference in the initial genetic makeup of SARS-CoV-2 in Spain compared with other European countries and show evidence to support the effectiveness of lockdown measures in controlling virus spread, even for the most successful genetic variants.

Published
2021

31. The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant

Author

López, Mariana G., Chiner-Oms, Álvaro, García de Viedma, Darío, Ruiz-Rodriguez, Paula, Bracho, Maria Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, de Marco, Griselda, García-González, Neris, Goig, Galo Adrian, Gómez-Navarro, Inmaculada, Jiménez-Serrano, Santiago, Martinez-Priego, Llúcia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Alberola, Juan, Albert, Eliseo, Aranzamendi Zaldumbide, Maitane, Bea-Escudero, María Pilar, Boga, Jose Antonio, Bordoy, Antoni E., Canut-Blasco, Andrés, Carvajal, Ana, Cilla Eguiluz, Gustavo, Cordón Rodríguez, Maria Luz, Costa-Alcalde, José J., de Toro, María, de Toro Peinado, Inmaculada, del Pozo, Jose Luis, Duchêne, Sebastián, Fernández-Pinero, Jovita, Fuster Escrivá, Begoña, Gimeno Cardona, Concepción, González Galán, Verónica, Gonzalo Jiménez, Nieves, Hernáez Crespo, Silvia, Herranz, Marta, Lepe, José Antonio, López-Causapé, Carla, López-Hontangas, José Luis, Martín, Vicente, Martró, Elisa, Milagro Beamonte, Ana, Montes Ros, Milagrosa, Moreno-Muñoz, Rosario, Navarro, David, Navarro-Marí, José María, Not, Anna, Oliver, Antonio, Palop-Borrás, Begoña, Parra Grande, Mónica, Pedrosa-Corral, Irene, Pérez González, Maria Carmen, Pérez-Lago, Laura, Pérez-Ruiz, Mercedes, Piñeiro Vázquez, Luis, Rabella, Nuria, Rezusta, Antonio, Robles Fonseca, Lorena, Rodríguez-Villodres, Ángel, Sanbonmatsu-Gámez, Sara, Sicilia, Jon, Soriano, Alex, Tirado Balaguer, María Dolores, Torres, Ignacio, Tristancho, Alexander, Marimón, José María, Pérez-Tur, Jordi, Catalán-Alonso, Pilar, Suárez González, Julia, Muñoz, Patricia, Ruiz-Rodríguez, Paula, Bracho, María Alma, Martínez Priego, Llúcia, Galán-Vendrell, Inmaculada, De Marco, Griselda, Ferrús-Abad, María Loreto, Carbó-Ramírez, Sandra, Nogueira, Jose Miguel, Camarena, Juan José, Martínez Expósito, Óscar, Antona Urieta, Nerea, Castelló-Abietar, Cristian, Rojo-Alba, Susana, Álvarez-Argüelles, Marta Elena, Melón, Santiago, Antuori, Adrián, Fernández-Navarro, Anabel, Lecaroz Agara, Maria Concepción, Gómez-González, Carmen, Aguirre-Quiñonero, Amaia, López-Mirones, José Israel, Fernández-Torres, Marina, Almela-Ferrer, Maria Rosario, Fregeneda-Grandes, Juan Miguel, Argüello, Héctor, Sorarrain, Ane, Trastoy, Rocío, Barbeito Castiñeiras, Gema, Coira, Amparo, Pérez del Molino, María Luisa, Aguilera, Antonio, Mediavilla Gradolph, Maria Concepción, Fernández-Alonso, Mirian, González-Recio, Oscar, Gutiérrez-Rivas, Mónica, Jiménez Clavero, Miguel Ángel, Ocete Mochón, María Dolores, Medina-Gonzalez, Rafael, Reina, Jordi, Gómez-Ruiz, Maria Dolores, Gonzalez-Barbera, Eva M., Molina, Antonio J., Fernandez-Villa, Tania, Martínez-Cameo, Nieves Felisa, Gracia-Grataloup, Yolanda, Tirado Balaguer, Maria Dolores, Gómez Alonso, Bárbara, Arjona Zaragozí, Francisco José, Chamizo López, Francisco Javier, Bordes-Benítez, Ana, Rabella, Núria, Navarro, Ferran, Miró, Elisenda, Simarro Córdoba, Encarnación, Lozano-Serra, Julia, Soriano, Álex, Roig Sena, Francisco Javier, Vanaclocha Luna, Hermelinda, Sanmartín, Isabel, García-Souto, Daniel, Pequeño-Valtierra, Ana, Tubio, Jose M. C., Temes, Javier, Rodríguez-Castro, Jorge, Santamarina García, Martín, Rodríguez-Iglesias, Manuel, Galán-Sanchez, Fátima, Rodríguez-Pallares, Salud, Azcona-Gutiérrez, José Manuel, Blasco-Alberdi, Miriam, Mayor, Alfredo, García-Basteiro, Alberto L., Moncunill, Gemma, Dobaño, Carlota, Cisteró, Pau, Mitjà, Oriol, González-Beiras, Camila, Vall-Mayans, Martí, Corbacho-Monné, Marc, Alemany, Andrea, Muñoz-Cuevas, Cristina, Rodríguez-Rodríguez, Guadalupe, Benito, Rafael, Algarate, Sonia, Bueno, Jessica, Vergara-Gómez, Andrea, Martínez, Miguel J., Vila, Jordi, Rubio, Elisa, Peiró-Mestres, Aida, Navero-Castillejos, Jessica, Posada, David, Valverde, Diana, Estévez, Nuria, Fernández-Silva, Iria, de Chiara, Loretta, Gallego-García, Pilar, Varela, Nair, Gómez-Pinedo, Ulises, Gozalo-Margüello, Mónica, Cano García, Maria Eliecer, Méndez-Legaza, José Manuel, Rodríguez-Lozano, Jesus, Siller, María, Pablo-Marcos, Daniel, Ruiz-García, Maria Montserrat, Galiana, Antonio, Sánchez-Almendro, Judith, Gascón Ros, Maria Isabel, Torregrosa-Hetland, Cristina Juana, Pastor Boix, Eva María, Cascales Ramos, Paloma, Garcinuño Enríquez, Pedro Luis, Raga Borja, Salvador, González Cantó, Julia, Martínez Macias, Olalla, de Salazar, Adolfo, Viñuela González, Laura, Chueca, Natalia, García, Federico, Gómez-Camarasa, Cristina, Farga Martí, Amparo, Falcón, Rocío, Domínguez-Márquez, Victoria, Planas, Anna M., Fernández-Cádenas, Israel, Marcos, Maria Ángeles, Ezpeleta, Carmen, Navascués, Ana, Miqueleiz Zapatero, Ana, Segovia, Manuel, Moreno-Docón, Antonio, Viedma, Esther, Recio Martínez, Raúl, Muñoz-Gallego, Irene, Gonzalez-Bodi, Sara, Folgueira, Maria Dolores, Mingorance, Jesús, Dahdouh, Elias, Lázaro-Perona, Fernando, Rodríguez-Tejedor, María, Romero-Gómez, María Pilar, García-Rodríguez, Julio, Galán, Juan Carlos, Rodríguez-Dominguez, Mario, Martínez-García, Laura, Abreu Di Berardino, Melanie, Ponce-Alonso, Manuel, González-Alba, Jose Maria, Sanz-Muñoz, Ivan, Pérez San José, Diana, Gil Fortuño, Maria, Bellido-Blasco, Juan B., Yagüe Muñoz, Alberto, Hernández Pérez, Noelia, Buj Jordá, Helena, Pérez Olaso, Óscar, González Praetorius, Alejandro, Martínez Ramírez, Nora Mariela, Ramírez Marinero, Aida, Padilla León, Eduardo, Vilas Basil, Alba, Canal Aranda, Mireia, Bernet Sánchez, Albert, Bellés Bellés, Alba, López González, Eric, Prats Sánchez, Iván, García-González, Mercè, Martínez-Lirola, Miguel José, Rodríguez Maresca, Manuel Ángel, Cabezas Fernández, Maria Teresa, Carrillo Gil, María Eugenia, Ventero Martín, Maria Paz, Molina Pardines, Carmen, Orta Mira, Nieves, Navarro Cots, María, Vidal Catalá, Inmaculada, García Nava, Isabel, Illescas Fernández-Bermejo, Soledad, Martínez-Alarcón, José, Torres-Narbona, Marta, Colmenarejo, Cristina, García-Agudo, Lidia, Pérez García, Jorge A., Yago López, Martín, Goberna Bravo, María Ángeles, Simón García, Victoria, Llop Furquet, Gonzalo, Iranzo Tatay, Agustín, Moreno-Marro, Sandra, Lozano Rodríguez, Noelia, Broseta Tamarit, Amparo, Badiola Díez, Juan José, Martínez-Ramírez, Amparo, Dopazo, Ana, Callejas, Sergio, Benguría, Alberto, Aguado, Begoña, Alcamí, Antonio, Bermejo Bermejo, Marta, Ramos-Ruíz, Ricardo, Fernández Soria, Víctor Manuel, Simón Soria, Fernando, Roig Cardells, Mercedes, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Research Council, European Commission, Generalitat Valenciana, Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula [0000-0003-0727-5974], D'Auria, Giuseppe [0000-0003-0672-2541], Gómez-Navarro, Inmaculada [0000-0002-5235-7365], Jiménez Serrano, Santiago [0000-0003-2917-6053], Aranzamendi Zaldumbide, Maitane [0000-0003-2432-7078], Boga, José Antonio [0000-0002-5500-9972], Bordoy, Antoni E. [0000-0002-1165-542X], Costa-Alcalde, José J. [0000-0002-1916-2216], Toro Peinado, Inmaculada de [0000-0002-8151-3275], López-Causapé, Carla [0000-0003-2228-2005], Martín, Vicente [0000-0003-0552-2804], Moreno-Muñoz, Rosario [0000-0002-0185-5612], Parra Grande, Mónica [0000-0002-8330-7467], Balaguer, María Dolores [0000-0003-3808-7300], Coscolla, Mireia [0000-0003-0752-0538], González-Candelas, Fernando [0000-0002-0879-5798], Comas, Iñaki [0000-0001-5504-9408], Ministerio de Ciencia (España), Generalitat Valenciana (España), Chiner-Oms, Álvaro, Ruiz-Rodríguez, Paula, D'Auria, Giuseppe, Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Aranzamendi Zaldumbide, Maitane, Boga, José Antonio, Bordoy, Antoni E., Costa-Alcalde, José J., Toro Peinado, Inmaculada de, López-Causapé, Carla, Martín, Vicente, Moreno-Muñoz, Rosario, Parra Grande, Mónica, Balaguer, María Dolores, Coscolla, Mireia, González-Candelas, Fernando, Comas, Iñaki, and Marimon, Jose Maria

Subjects
DYNAMICS, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Physical Distancing, Biology, Severity of Illness Index, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Pandemic, Quarantine, Genetics, Humans, Clade, Phylogeny, 030304 developmental biology, 0303 health sciences, Models, Statistical, SARS-CoV-2, Incidence (epidemiology), Incidence, Genetic variants, COVID-19, Genomics, New variant, Dynamics, Virus, 3. Good health, Spain, Communicable Disease Control, VIRUS, 030217 neurology & neurosurgery, Demography
Abstract

SeqCOVID-Spain consortium: Álvaro Chiner-Oms, Irving Cancino-Muñoz, Mariana G. López, Manuela Torres-Puente, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Jordi Pérez-Tur, Darío García de Viedma, Laura Pérez-Lago, Marta Herranz, Jon Sicilia, Pilar Catalán-Alonso, Julia Suárez González, Patricia Muñoz, Mireia Coscolla, Paula Ruiz-Rodríguez, Fernando González-Candelas, Iñaki Comas, Lidia Ruiz-Roldán, María Alma Bracho, Neris García-González, Llúcia Martínez Priego, Inmaculada Galán-Vendrell, Paula Ruiz-Hueso, Griselda De Marco, María Loreto Ferrús-Abad, Sandra Carbó-Ramírez, Giuseppe D’Auria, Galo Adrian Goig, Juan Alberola, Jose Miguel Nogueira, Juan José Camarena, David Navarro, Eliseo Albert, Ignacio Torres, Maitane Aranzamendi Zaldumbide, Óscar Martínez Expósito, Nerea Antona Urieta, María de Toro, María Pilar Bea-Escudero, Jose Antonio Boga, Cristian Castelló-Abietar, Susana Rojo-Alba, Marta Elena Álvarez-Argüelles, Santiago Melón, Elisa Martró, Antoni E. Bordoy, Anna Not, Adrián Antuori, Anabel Fernández-Navarro, Andrés Canut-Blasco, Silvia Hernáez Crespo, Maria Luz Cordón Rodríguez, Maria Concepción Lecaroz Agara, Carmen Gómez-González, Amaia Aguirre-Quiñonero, José Israel López-Mirones, Marina Fernández-Torres, Maria Rosario Almela-Ferrer, Ana Carvajal, Juan Miguel Fregeneda-Grandes, Héctor Argüello, Gustavo Cilla Eguiluz, Milagrosa Montes Ros, Luis Piñeiro Vázquez, Ane Sorarrain, José María Marimón, José J. Costa-Alcalde, Rocío Trastoy, Gema Barbeito Castiñeiras, Amparo Coira, María Luisa Pérez del Molino, Antonio Aguilera, Begoña Palop-Borrás, Inmaculada de Toro Peinado, Maria Concepción Mediavilla Gradolph, Mercedes Pérez-Ruiz, Mirian Fernández-Alonso, Jose Luis del Pozo, Oscar González-Recio, Mónica Gutiérrez-Rivas, Jovita Fernández-Pinero, Miguel Ángel Jiménez Clavero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, María Dolores Ocete Mochón, Rafael Medina-Gonzalez, José Antonio Lepe, Verónica González Galán, Ángel Rodríguez-Villodres, Nieves Gonzalo Jiménez, Jordi Reina, Carla López-Causapé, Maria Dolores Gómez-Ruiz, Eva M. Gonzalez-Barbera, José Luis López-Hontangas, Vicente Martín, Antonio J. Molina, Tania Fernandez-Villa, Ana Milagro Beamonte, Nieves Felisa Martínez-Cameo, Yolanda Gracia-Grataloup, Rosario Moreno-Muñoz, Maria Dolores Tirado Balaguer, José María Navarro-Marí, Irene Pedrosa-Corral, Sara Sanbonmatsu-Gámez, Antonio Oliver, Mónica Parra Grande, Bárbara Gómez Alonso, Francisco José Arjona Zaragozí, Maria Carmen Pérez González, Francisco Javier Chamizo López, Ana Bordes-Benítez, Núria Rabella, Ferran Navarro, Elisenda Miró, Antonio Rezusta, Alexander Tristancho, Encarnación Simarro Córdoba, Julia Lozano-Serra, Lorena Robles Fonseca, Álex Soriano, Francisco Javier Roig Sena, Hermelinda Vanaclocha Luna, Isabel Sanmartín, Daniel García-Souto, Ana Pequeño-Valtierra, Jose M. C. Tubio, Javier Temes, Jorge Rodríguez-Castro, Martín Santamarina García, Manuel Rodríguez-Iglesias, Fátima Galán-Sanchez, Salud Rodríguez-Pallares, José Manuel Azcona-Gutiérrez, Miriam Blasco-Alberdi, Alfredo Mayor, Alberto L. García-Basteiro, Gemma Moncunill, Carlota Dobaño, Pau Cisteró, Oriol Mitjà, Camila González-Beiras, Martí Vall-Mayans, Marc Corbacho-Monné, Andrea Alemany, Cristina Muñoz-Cuevas, Guadalupe Rodríguez-Rodríguez, Rafael Benito, Sonia Algarate, Jessica Bueno, Andrea Vergara-Gómez, Miguel J. Martínez, Jordi Vila, Elisa Rubio, Aida Peiró-Mestres, Jessica Navero-Castillejos, David Posada, Diana Valverde, Nuria Estévez, Iria Fernández-Silva, Loretta de Chiara, Pilar Gallego-García, Nair Varela, Ulises Gómez-Pinedo, Mónica Gozalo-Margüello, Maria Eliecer Cano García, José Manuel Méndez-Legaza, Jesus Rodríguez-Lozano, María Siller, Daniel Pablo-Marcos, Maria Montserrat Ruiz-García, Antonio Galiana, Judith Sánchez-Almendro, Maria Isabel Gascón Ros, Cristina Juana Torregrosa-Hetland, Eva María Pastor Boix, Paloma Cascales Ramos, Pedro Luis Garcinuño Enríquez, Salvador Raga Borja, Julia González Cantó, Olalla Martínez Macias, Adolfo de Salazar, Laura Viñuela González, Natalia Chueca, Federico García, Cristina Gómez-Camarasa, Amparo Farga Martí, Rocío Falcón, Victoria Domínguez-Márquez, Anna M. Planas, Israel Fernández-Cádenas, Maria Ángeles Marcos, Carmen Ezpeleta, Ana Navascués, Ana Miqueleiz Zapatero, Manuel Segovia, Antonio Moreno-Docón, Esther Viedma, Raúl Recio Martínez, Irene Muñoz-Gallego, Sara Gonzalez-Bodi, Maria Dolores Folgueira, Jesús Mingorance, Elias Dahdouh, Fernando Lázaro-Perona, María Rodríguez-Tejedor, María Pilar Romero-Gómez, Julio García-Rodríguez, Juan Carlos Galán, Mario Rodríguez-Dominguez, Laura Martínez-García, Melanie Abreu Di Berardino, Manuel Ponce-Alonso, Jose Maria González-Alba, Ivan Sanz-Muñoz, Diana Pérez San José, Maria Gil Fortuño, Juan B. Bellido-Blasco, Alberto Yagüe Muñoz, Noelia Hernández Pérez, Helena Buj Jordá, Óscar Pérez Olaso, Alejandro González Praetorius, Nora Mariela Martínez Ramírez, Aida Ramírez Marinero, Eduardo Padilla León, Alba Vilas Basil, Mireia Canal Aranda, Albert Bernet Sánchez, Alba Bellés Bellés, Eric López González, Iván Prats Sánchez, Mercè García-González, Miguel José Martínez-Lirola, Manuel Ángel Rodríguez Maresca, Maria Teresa Cabezas Fernández, María Eugenia Carrillo Gil, Maria Paz Ventero Martín, Carmen Molina Pardines, Nieves Orta Mira, María Navarro Cots, Inmaculada Vidal Catalá, Isabel García Nava, Soledad Illescas Fernández-Bermejo, José Martínez-Alarcón, Marta Torres-Narbona, Cristina Colmenarejo, Lidia García-Agudo, Jorge A. Pérez García, Martín Yago López, María Ángeles Goberna Bravo, Victoria Simón García, Gonzalo Llop Furquet, Agustín Iranzo Tatay, Sandra Moreno-Marro, Noelia Lozano Rodríguez, Amparo Broseta Tamarit, Juan José Badiola Díez, Amparo Martínez-Ramírez, Ana Dopazo, Sergio Callejas, Alberto Benguría, Begoña Aguado, Antonio Alcamí, Marta Bermejo Bermejo, Ricardo Ramos-Ruíz, Víctor Manuel Fernández Soria, Fernando Simón Soria & Mercedes Roig Cardells, The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events. Both SECs were related closely to the initial Asian variants of SARS-CoV-2 and spread widely across Spain. We inferred a substantial reduction in the effective reproductive number of both SECs due to public-health interventions (Re, This work was mainly funded by the Instituto de Salud Carlos III project COV20/00140, with additional funding by Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia project PID2019-104477RB-100, ERC StG 638553 and ERC CoG 101001038 to I.C., and BFU2017-89594R to F.G.C. M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and Generalitat Valenciana (Regional Government) project SEJI/2019/011. We gratefully acknowledge Hospital Universitari Vall d’Hebron, Instituto de Salud Carlos III, IrsiCaixa AIDS Research Lab and all the international researchers and institutions that submitted sequenced SARS-CoV-2 genomes to the GISAID’s EpiCov Database (Supplementary Table 1), as an important part of our analyses has been made possible by the sharing of their work. We also thank Unidad de Bioinformática y Estadística, Centro de Investigación Príncipe Felipe, for allowing us to use the Computer Cluster to perform some of the bioinformatic analysis.

Published
2021

32. Supplementary Materials: In silico exploration of Mycobacterium tuberculosis metabolic networks shows host-associated convergent fluxomic phenotypes

Author

Santamaria, Guillem, Ruiz-Rodríguez, Paula, Renau-Mínguez, Chantal, Pinto, Francisco R., Coscollá, Mireia, Santamaria, Guillem, Ruiz-Rodríguez, Paula, Renau-Mínguez, Chantal, Pinto, Francisco R., and Coscollá, Mireia

Abstract

Figure S1: Correspondence Analysis of all the potentially deleterious SNPs, Figure S2: Unsupervised analysis of the deletion data of the genes included in iEK1011 2.0 genome-scale metabolic model, Figure S3: Principal Component Analysis of FBA flux distributions of the lineage-specific genome-scale metabolic models, Figure S4: Principal Component Analysis of the sampled solution space of each one of the lineage-specific genome-scale metabolic models, Figure S5: OPLS-DA loadings for the significantly altered subsystems between animal- and human-associated sampled models, Figure S6: Difference of exchange fluxes between sampled models and FBA flux distribution of metabolites in Middlebrock 7H9 OADC + cholesterol for each lineage’s model, Table S1: Illumina genomes information, Table S2: iEK1011 2.0 reaction information, Table S3: Removed reactions per lineage model, Table S4: OPLS-DA variable coefficients, Table S5: Statistically significant reaction fluxes between samples of animal- and human-associated models, File S1: Description of the genes removed from iEK1011 2.0 to generate lineage-specific GEMs, File S2: Lineage-specific genome scale metabolic models.

Published
2022

33. Supplementary Information: 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, Wieczor, Milosz, Mata, Carlos P., Krieger, James, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, Carazo, José M., Ginex, Tiziana, Marco-Marín, Clara, Wieczor, Milosz, Mata, Carlos P., Krieger, James, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, and Carazo, José M.

Published
2022

34. The 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, Wieczor, Milosz, Mata, Carlos P., Krieger, James, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, Carazo, José M., Ginex, Tiziana, Marco-Marín, Clara, Wieczor, Milosz, Mata, Carlos P., Krieger, James, Ruiz-Rodríguez, Paula, López-Redondo, Marisa, Francés-Gómez, Clara, Melero, Roberto, Sorzano, Carlos Óscar S., Martínez, Marta, Gougeard, Nadine, Forcada-Nadal, Alicia, Zamora-Caballero, Sara, Gozalbo-Rovira, Roberto, Sanz-Frasquet, Carla, Arranz, Rocío, Bravo, Jerónimo, Rubio, Vicente, Marina, Alberto, The IBV-Covid19-Pipeline, Geller, Ron, Comas, Iñaki, Gil, Carmen, Coscollá, Mireia, Orozco, Modesto, Llácer, José Luis, and Carazo, José M.

Published
2022

35. Real-time surveillance of SARS-CoV-2: surveying mixtures of lineage- defining markers

Author

Álvarez-Herrera, Miguel, Navarro-Domínguez, Beatriz, Ruiz-Rodríguez, Paula, Bracho, María Alma, Chiner-Oms, Álvaro, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Álvarez-Herrera, Miguel, Navarro-Domínguez, Beatriz, Ruiz-Rodríguez, Paula, Bracho, María Alma, Chiner-Oms, Álvaro, González-Candelas, Fernando, Comas, Iñaki, and Coscollá, Mireia

Published
2022

36. Evolutionary genomics of SARS-CoV-2: keys for viral success

Author

Álvarez-Herrera, Miguel, Carazo, José M., Comas, Iñaki, Coscollá, Mireia, Elena, Santiago F., Francés-Gómez, Clara, Franco, María Luisa, García Rasines, Daniel, Geller, Ron, Gil, Carmen, González-Candelas, Fernando, Hillung, Julia, Llácer, José Luis, Marina, Alberto, Marqués, M. Carmen, Naveiro Flores, Roi, Ríos, David, Rodríguez Santana, Simón, Ruiz-Rodríguez, Paula, Sorzano, Carlos Óscar S., Ulzurum, Eugenia, Vilar, Marçal, Álvarez-Herrera, Miguel, Carazo, José M., Comas, Iñaki, Coscollá, Mireia, Elena, Santiago F., Francés-Gómez, Clara, Franco, María Luisa, García Rasines, Daniel, Geller, Ron, Gil, Carmen, González-Candelas, Fernando, Hillung, Julia, Llácer, José Luis, Marina, Alberto, Marqués, M. Carmen, Naveiro Flores, Roi, Ríos, David, Rodríguez Santana, Simón, Ruiz-Rodríguez, Paula, Sorzano, Carlos Óscar S., Ulzurum, Eugenia, and Vilar, Marçal

Published
2022

37. Genomic surveillance and impact of SARS-CoV-2 mutations

Author

Ruiz-Rodríguez, Paula, Álvarez-Herrera, Miguel, Franco, María Luisa, Francés-Gómez, Clara, Marqués, M. Carmen, Hillung, Julia, Ulzurrun, Eugenia, Martínez-Martínez, Francisco José, Rodríguez Santana, Simón, Naveiro Flores, Roi, García Rasines, Daniel, Marina, Alberto, Llácer, José Luis, Vilar, Marçal, Sorzano, Carlos Óscar S., Campillo, Nuria E., Rubio, Vicente, Carazo, José M., Gil, Carmen, González-Candelas, Fernando, Geller, Ron, Comas, Iñaki, Elena, Santiago F., Coscollá, Mireia, Ruiz-Rodríguez, Paula, Álvarez-Herrera, Miguel, Franco, María Luisa, Francés-Gómez, Clara, Marqués, M. Carmen, Hillung, Julia, Ulzurrun, Eugenia, Martínez-Martínez, Francisco José, Rodríguez Santana, Simón, Naveiro Flores, Roi, García Rasines, Daniel, Marina, Alberto, Llácer, José Luis, Vilar, Marçal, Sorzano, Carlos Óscar S., Campillo, Nuria E., Rubio, Vicente, Carazo, José M., Gil, Carmen, González-Candelas, Fernando, Geller, Ron, Comas, Iñaki, Elena, Santiago F., and Coscollá, Mireia

Published
2022

38. In silico exploration of Mycobacterium tuberculosis metabolic networks shows host-associated convergent fluxomic phenotypes

Author

Fundação para a Ciência e a Tecnologia (Portugal), European Commission, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Generalitat Valenciana, Santamaria, Guillem, Ruiz-Rodríguez, Paula, Renau-Mínguez, Chantal, Pinto, Francisco R., Coscollá, Mireia, Fundação para a Ciência e a Tecnologia (Portugal), European Commission, Consejo Superior de Investigaciones Científicas (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Generalitat Valenciana, Santamaria, Guillem, Ruiz-Rodríguez, Paula, Renau-Mínguez, Chantal, Pinto, Francisco R., and Coscollá, Mireia

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, is composed of several lineages characterized by a genome identity higher than 99%. Although the majority of the lineages are associated with humans, at least four lineages are adapted to other mammals, including different M. tuberculosis ecotypes. Host specificity is associated with higher virulence in its preferred host in ecotypes such as M. bovis. Deciphering what determines the preference of the host can reveal host-specific virulence patterns. However, it is not clear which genomic determinants might be influencing host specificity. In this study, we apply a combination of unsupervised and supervised classification methods on genomic data of ~27,000 M. tuberculosis clinical isolates to decipher host-specific genomic determinants. Host-specific genomic signatures are scarce beyond known lineage-specific mutations. Therefore, we integrated lineage-specific mutations into the iEK1011 2.0 genome-scale metabolic model to obtain lineage-specific versions of it. Flux distributions sampled from the solution spaces of these models can be accurately separated according to host association. This separation correlated with differences in cell wall processes, lipid, amino acid and carbon metabolic subsystems. These differences were observable when more than 95% of the samples had a specific growth rate significantly lower than the maximum achievable by the models. This suggests that these differences might manifest at low growth rate settings, such as the restrictive conditions M. tuberculosis suffers during macrophage infection.

Published
2022

40. Evolution, virulence and immunogenicity of relevant SARS-CoV-2 spike mutants

Author

Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki, Chiner-Oms, Álvaro, Comas, Iñaki [0000-0001-5504-9408], and Chiner-Oms, Álvaro [0000-0002-0463-0101]

Abstract

SeqCOVm-SPAIN consortium., Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021., We have detected two mutations in the Spike protein of SARS-CoV-2 sequences at amino acid positions 1163 and 1167 which appeared independently in multiple transmission clusters and different genetic backgrounds, indicating they may increase viral fitness. Both mutations appeared together in a cluster within clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information of the S protein in the preand post-fusion conformations we predict that both mutations confer rigidity, that potentially could decrease viral fitness. Despite the multiple and successful appearance of two HR2 mutations during the first year of SARS-CoV-2 evolution, in vi tro stability, infectivi ty, or antibody escape does not seem to play a role., This work was funded by the Instituto de Salud Carlos III project COV2o/o0140 and COV2o/o0437• Spanish National Research Council project CSIC"COV19~021 and CSIC-COVID19-082, and the Generalitat Valenciana (SEJI/2019/011 and Covid 19-SCI).Action co-financed by the European Union through the Operational Program of the European Regional Development Fund (ERDF) ofthe Valencian Community 2014-2020. MC is supported by Ramón y Caja/program from Ministerio de Ciencia, grant RTI2018-094399-A-Joo.

Published
2021

41. Integrating genomics and infection biology to decipher differences between human and animal associated M. tuberculosis lineages

Author

Santamaria, Guillem, Renau-Mínguez, Chantal, Gomis, Carlos, Espert, Antonio, Buksa, Nikolina, Ruiz-Rodríguez, Paula, Pinto, Francisco R., Coscollá, Mireia, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat Valenciana, and European Commission

Abstract

Resumen del póster presentado al XLII Congreso de la Sociedad Española de Genética, celebrado de forma virtual del 14 al 18 de junio de 2021., Mycobacterium tuberculosis, which causes tuberculosis, is of the top 10 causes of death worldwide caused by an infectious disease. The majority of the lineages infect predominantly humans, except four lineages that infect a wide range of other mammals, and we refer to as animal-associated lineages. Because understanding the genetic basis of host specificity can inform about the virulence factors of M. tuberculosis in each host, our objective is to decipher is host specificity correlates with virulence in vitro, and with lineage specific genomic signatures. We combined experiments in macrophage infection model with whole genome sequencing analysis of 35.000 clinical M. tuberculosis strains representing all ecotypes to determine genomic specific signatures of the bacteria during the infectious process. We observed different genomics signatures between human and animal M. tuberculosis associated lineages. A differential signature was observed in three of the four genes that encode for phospholipase C in M. tuberculosis, lost in three out of four animal lineages, and present in the human lineages. Phylogenomic analysis showed that these deletions happened several times during evolution indicating a convergence in the loss of these regions that could be under differential selection pressure in animal and human associated strains. Because phospholipase C has been previously linked to M. tuberculosis virulence, we explored the differential expression of these genes between lineages infecting two different host cells., M.C. is supported by Ramón y Cajal program from Ministerio de Ciencia. This work was funded by Generalitat Valenciana (SEJI/2019/011) and Ministerio de ciencia e innovación (RTI2018-094399-A-I00).

Published
2021

42. The SeqCOVID-Spain consortium: unravelling the dynamics of the COVID-19 first epidemic wave in Spain

Author

Chiner-Oms, Álvaro, López, Mariana G., García de Viedma, Darío, Ruiz-Rodríguez, Paula, Bracho, María Alma, Cancino-Muñoz, Irving, D’Auria, Giuseppe, Marco, Griselda de, García-González, Neris, Goig, Galo A., Gómez-Navarro, Inmaculada, Jiménez Serrano, Santiago, Martínez-Priego, Llucia, Ruiz-Hueso, Paula, Ruiz-Roldán, Lidia, Torres-Puente, Manuela, Coscollá, Mireia, González-Candelas, Fernando, Comas, Iñaki, Seqcovid-Spain Consortium, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Consejo Superior de Investigaciones Científicas (España), European Research Council, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki

Abstract

Póster presentado a la Applied Bioinformatics and Public Health Microbiology 2021 Virtual Conference, celebrada del 5 al 7 de mayo de 2021., The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinary consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain, representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initialintroductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid-March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of pre-existing SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants., This work was funded by the Instituto de Salud Carlos III project COV20/00140, Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia PID2019-104477RB-I00 and ERC StG 638553 to IC, and BFU2017-89594R to FGC. MC is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and SEJI/2019/011.

Published
2021

43. Emergence of adaptive mutations of the spike In SARS-CoV-2

Author

Ruiz-Rodríguez, Paula, Francés-Gómez, Clara, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, Bracho, María Alma, D'Auria, Giuseppe, González-Candelas, Fernando, Geller, Ron, Comas, Iñaki, and Seqcovid-Spain Consortium

Abstract

Resumen del trabajo presentado al II Congreso Nacional Covid-19, celebrado de forma virtual del 12 al 16 de abril de 2021., Surveillance of mutants of SARS-CoV-2 aims to monitor the appearance of new variants that could potentially change the biological properties of the virus. During the first year of SARS-CoV-2 evolution, different variants have been detected with different degrees of biological impact on the virus and also on the epidemic. We have detected two mutations of the spike protein of SARS-CoV-2 that have appeared independently multiple times in different genetic backgrounds and hosts, possibly indicating they could increase viral fitness. Interestingly, when both mutations appeared together, the genotype increased in frequency more than the individual mutants. This variant that we call Variant of Interest 1 and includes 12 other single nucleotide polymorphisms but no deletions with respect to the reference genome. VOI.1 appeared after the First epidemic Wave in Spain, and subsequently migrated and increased in frequency in 8 countries. VOI.1 includes a cluster of sequences that have acquired the concerning mutation E484K, which could result in antibody escape. We explored if these two mutations confer a greater capacity to the virus to produce more particles. Unexpectedly, we find a reduction in infectivity of this variant versus the 20EU1 in two different cell lines. However, clinical results differ slightly and we found that individuals infected with VOI.1 have similar levels of viral RNA in nasopharyngeal swabs than patients infected with 20EU1 variants, both of them significantly higher than non 20EU1 lineages. Finally, in order to assess the risk of VOI.1 because of antibody escape, we explored the impact on immunogenicity. A moderate but significant reduction in sensitivity to neutralization by sera from convalescent donors obtained from the early period of the pandemic was observed. Overall we could detect and monitor the spread of a variant of interest which could pose a potential risk. The expansion of such variants has allowed the acquisition of another potentially risky mutation, present in other variants of concern, which could pose an additional threat.

Published
2021

44. Defining antigenic variation in Mycobacterium tuberculosis ecotypes

Author

Ruiz-Rodríguez, Paula and Coscollá, Mireia

Abstract

Resumen del trabajo presentado al 41st Annual Congress of the European Society of Mycobacteriology (ESM), celebrado de forma virtual del 28 al 29 de junio de 2019., Most known pathogens usually adopt the antigenic variation strategy where the host and the microorganism establish an evolutionary arms race, where each of the individuals acquires new improvements to overcome the opponent, setting a balance between them. In the case of Mycobacterium tuberculosis, it is unknown whether the antigenic variation could be behind the ability to evade the immune system. In this study, we identified genomic variation in 3,480 experimentally verified epitopes of T and B cells recognized from 3 different hosts: human, bovine, and murine, over 13,451 non-duplicated genomes from clinical strains representing different M. tuberculosis lineages. We studied how diversity could impact epitope recognition through analysing SNPs, deletions and genetic disruptions. Additionally, we analysed populations by phylogenomics to identify possible evolutionary convergences within ecotypes and host range. We observed that regions harbouring epitopes are more mutated than other regions of the genome. Moreover, we found that human-associated Lineage 4 contained the most diverse T cell epitopes compared with Lineage 2 which showed the most diverse B cell epitopes. In order to verify if highly variable epitopes have immunological consequences, analysis including immunologic experiments in individual epitopes will be conducted.

Published
2021

45. Decyphering Mycobacterium tuberculosis host specificity through the integration of genomics and infection biology

Author

Santamaria, Guillem, Renau-Mínguez, Chantal, Gomis, Carlos, Espert, Antonio, Buksa, Nikolina, Ruiz-Rodríguez, Paula, Pinto, Filipe, and Coscollá, Mireia

Abstract

Resumen del póster presentado al 41st Annual Congress of the European Society of Mycobacteriology (ESM), celebrado de forma virtual del 28 al 29 de junio de 2019., Mycobacterium tuberculosis is the microorganism that produces tuberculosis, which is among the top 10 causes of death worldwide. Most of its lineages infect predominantly humans, except for four, which infect a wide range of other mammals. We will refer to them as animal-associated lineages. As understanding the genetic basis of host specificity can inform about the virulence factors of M. tuberculosis in each host, our objective is to decipher if host specificity correlates with virulence in vitro, and with lineage specific genomic signatures. We combined experiments in macrophage infection model with whole genome sequencing analysis of ~35.000 clinical M. tuberculosis strains to determine genomic specific signatures of the bacteria during the infectious process. We observed different genomic signatures between human and animal M. tuberculosis associated lineages. A differential signature was observed in three of the four genes that encode for phospholipase C in M. tuberculosis (plcABC) and PPE38. These genes are part of a previously described Region of Difference (RD), RD5, which is unevenly distributed between animal- and human-associated lineages. This region is completely lost in two and partially lost in one out of four of the animal lineages, while present in most of the isolates belonging to the human-associated lineages. Phylogenomic analysis showed that these deletions happened several times during evolution indicating the loss of these regions could be under differential selection pressure in animal- and human-associated strains. Because phospholipase C has been previously linked to M. tuberculosis virulence, we explored the differential expression of these genes between lineages infecting macrophages coming from different hosts.

Published
2021

46. Exploring the genome of Mycobacterium brumae, a species of bacterium with therapeutic potential

Author

Renau-Mínguez, Chantal, Herrero-Abadía, Paula, Sentandreu, Vicente, Ruiz-Rodríguez, Paula, Goig, Galo A., Comas, Iñaki, Julián, Esther, Coscollá, Mireia, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Generalitat Valenciana, and Generalitat de Catalunya

Abstract

Resumen del trabajo presentado al XLII Congreso de la Sociedad Española de Genética (SEG), celebrado de forma virtual del 14 al 18 de junio de 2021., This work was supported by RTI2018-094399-A-I00, RTI2018-098777-B-I00 and 2017SGR-229.

Published
2021

47. Genomic determinants associated with SARS-CoV-2 virulence

Author

Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Comas, Iñaki, Torres-Puente, Manuela, López, Mariana G., and Chiner-Oms, Álvaro

Abstract

Trabajo presentado al 31st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), celebrado online del 9 al 12 de julio de 2021., This work was funded by the Instituto de Salud Carlos III project COV2o/oo140 and COV2o/ o0437,Spanish National Research Council project CSIC­ COV19·0l1 and CSIC-COVID19-082,and the Generalitat Valenciana (SEJI/2019/011 and Covid_19-SCI).Action co-financed by the European Union through the Operatianal Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020.MC is supported by Ramón y Cajal program from Ministerio de Ciencia,grant RTI2018-094399-A-I00.

Published
2021

48. New insights in the genome content of the bacterium Mycobacterium brumae

Author

Renau-Mínguez, Chantal, Herrero-Abadía, Paula, Sentandreu, Vicente, Ruiz-Rodríguez, Paula, Goig, Galo A., Comas, Iñaki, Julián, Esther, and Coscollá, Mireia

Abstract

Resumen del póster presentado al 41st Annual Congress of the European Society of Mycobacteriology (ESM), celebrado de forma virtual del 28 al 29 de junio de 2019., Mycobacterium brumae is a fast-growing, non-pathogenic Mycobacterium species, originally isolated from environmental and human samples in Barcelona, Spain. Previous studies have shown that the implementation of non-pathogenic mycobacteria, such as Mycobacterium bovis BCG can improve the treatment against high-risk non-muscle invasive bladder cancer (BC) by intravesical administration. M. brumae has been shown to be non-pathogenic and its phenotype and immunogenic effect have been well characterized. However, the knowledge of its underlying genetic composition is still incomplete. In this study we have sequenced the genome by means of PACBIO of the M. brumae strain CR-270 obtaining the most complete assembly to date. We describe its genetic content by showing evolutionary relationships between different mycobacteria and we compare its virulence gene content with other virulent mycobacteria such as H37Rv reference strain. Furthermore, we describe the genetic variability of M. brumae by comparative genomics using obtained Illumina sequences. Our results contribute to increase the knowledge about the genetic bases that explain the non-pathogenic phenotype of this bacterium with therapeutic potential.

Published
2021

49. Genomic determinants associated with SARS-CoV-2 virulence

Author

Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, Coscollá, Mireia, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Torres-Puente, Manuela [0000-0002-8352-180X], López, Mariana G. [0000-0002-2216-9232], Chiner-Oms, Álvaro [0000-0002-0463-0101], Ruiz-Rodríguez, Paula, Chaturvedi, N., Bracho, María Alma, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, López, Mariana G., Cancino-Muñoz, Irving, Ruiz-Hueso, Paula, Torres-Puente, Manuela, D’auria, M., Martínez-Priego, Llucia, González-Candelas, Fernando, Comas, Iñaki, and Coscollá, Mireia

Published
2021

50. Evolution, virulence and immunogenicity of relevant SARS-CoV-2 spike mutants

Author

Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, Comas, Iñaki, Instituto de Salud Carlos III, Consejo Superior de Investigaciones Científicas (España), Generalitat Valenciana, Ministerio de Ciencia e Innovación (España), Comas, Iñaki [0000-0001-5504-9408], Chiner-Oms, Álvaro [0000-0002-0463-0101], Coscollá, Mireia, Ruiz-Rodríguez, Paula, Francés-Cuesta, Carlos, Geller, Ron, Chiner-Oms, Álvaro, Jiménez-Serrano, Santiago, Marina, Alberto, Martínez-Priego, Llucia, D'Auria, Giuseppe, López, Mariana G., Cancino-Muñoz, Irving, Torres-Puente, Manuela, Bracho, María Alma, Ruiz-Hueso, Paula, González-Candelas, Fernando, and Comas, Iñaki

Abstract

We have detected two mutations in the Spike protein of SARS-CoV-2 sequences at amino acid positions 1163 and 1167 which appeared independently in multiple transmission clusters and different genetic backgrounds, indicating they may increase viral fitness. Both mutations appeared together in a cluster within clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information of the S protein in the preand post-fusion conformations we predict that both mutations confer rigidity, that potentially could decrease viral fitness. Despite the multiple and successful appearance of two HR2 mutations during the first year of SARS-CoV-2 evolution, in vi tro stability, infectivi ty, or antibody escape does not seem to play a role.

Published
2021

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