Pilar Somovilla

Mrs. Pilar Somovilla

Biología Molecular, Universidad Autónoma de Madrid, Madrid, Spain
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orcid

Research Focus & Metrics

Academic Career Length

11Years (2016-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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8 June 2022 in Pathogens
Verified
Journal Article
Open access
PDF file
BMBrenda Martínez-González
Brenda Martínez-González
MSMaría Eugenia Soria
María Eugenia Soria
LVLucía Vázquez-Sirvent
Lucía Vázquez-Sirvent
CFCristina Ferrer-Orta
Cristina Ferrer-Orta
RLRebeca Lobo-Vega
Rebeca Lobo-Vega
CPCelia Perales
Celia Perales
Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50- to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussed.

21 December 2023 in Journal of Virology
Verified
Journal Article
Closed access
EDEsteban Domingo
Esteban Domingo
BMBrenda Martínez-González
Brenda Martínez-González
CGCarlos García-Crespo
Carlos García-Crespo
Pilar SomovillaPilar Somovilla
Pilar Somovilla
AÁAna Isabel de Ávila
Ana Isabel de Ávila
CPCelia Perales
Celia Perales
Upon the emergence of SARS-CoV-2 in the human population, it was conjectured that for this coronavirus the dynamic intra-host heterogeneity typical of RNA viruses would be toned down. Nothing of this sort is observed. Here we review the main observations on the complexity and diverse composition of SARS-CoV-2 mutant spectra sampled from infected patients, within the framework of quasispecies dynamics. The analyses suggest that the information provided by myriads of genomic sequences within infected individuals may have a predictive value of the genomic sequences that acquire epidemiological relevance. Possibilities to reconcile the presence of broad mutant spectra in the large RNA coronavirus genome with its encoding a 3’ to 5’ exonuclease proofreading-repair activity are considered. Indeterminations in the behavior of individual viral genomes provide a benefit for the survival of the ensemble. We propose that this concept falls in the domain of “stochastic thinking,” a notion that applies also to cellular processes, as a means for biological systems to face unexpected needs.

14 April 2024 in British Journal of Pharmacology
Verified
Journal Article
Closed access
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CGCarlos García‐Crespo
Carlos García‐Crespo
AÁAna Isabel de Ávila
Ana Isabel de Ávila
IGIsabel Gallego
Isabel Gallego
MSMaría Eugenia Soria
María Eugenia Soria
ADAntoni Durán‐Pastor
Antoni Durán‐Pastor
CPCelia Perales
Celia Perales

28 February 2024 in Proceedings of the National Academy of Sciences
Verified
Journal Article
Open access
SDSoledad Delgado
Soledad Delgado
Pilar SomovillaPilar Somovilla
Pilar Somovilla
CFCristina Ferrer-Orta
Cristina Ferrer-Orta
BMBrenda Martínez-González
Brenda Martínez-González
SVSergi Vázquez-Monteagudo
Sergi Vázquez-Monteagudo
EDEsteban Domingo
Esteban Domingo
Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.

18 June 2019 in Pathogens
Verified
Journal Article
Open access
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Pilar SomovillaPilar Somovilla
Pilar Somovilla
SMSusanna Manrubia
Susanna Manrubia
ELEster Lázaro
Ester Lázaro
The rate of change in selective pressures is one of the main factors that determines the likelihood that populations can adapt to stress conditions. Generally, the reduction in the population size that accompanies abrupt environmental changes makes it difficult to generate and select adaptive mutations. However, in systems with high genetic diversity, as happens in RNA viruses, mutations with beneficial effects under new conditions can already be present in the population, facilitating adaptation. In this work, we have propagated an RNA bacteriophage (Qβ) at temperatures higher than the optimum, following different patterns of change. We have determined the fitness values and the consensus sequences of all lineages throughout the evolutionary process in order to establish correspondences between fitness variations and adaptive pathways. Our results show that populations subjected to a sudden temperature change gain fitness and fix mutations faster than those subjected to gradual changes, differing also in the particular selected mutations. The life-history of populations prior to the environmental change has great importance in the dynamics of adaptation. The conclusion is that in the bacteriophage Qβ, the standing genetic diversity together with the rate of temperature change determine both the rapidity of adaptation and the followed evolutionary pathways.

24 January 2023 in Antimicrobial Agents and Chemotherapy
Verified
Journal Article
Closed access
Pilar SomovillaPilar Somovilla
Pilar Somovilla
CGCarlos García-Crespo
Carlos García-Crespo
BMBrenda Martínez-González
Brenda Martínez-González
MSMaría Eugenia Soria
María Eugenia Soria
AÁAna Isabel de Ávila
Ana Isabel de Ávila
CPCelia Perales
Celia Perales
We report that ribavirin exerts an inhibitory and mutagenic activity on SARS-CoV-2-infecting Vero cells, with a therapeutic index higher than 10. Deep sequencing analysis of the mutant spectrum of SARS-CoV-2 replicating in the absence or presence of ribavirin indicated an increase in the number of mutations, but not in deletions, and modification of diversity indices, expected from a mutagenic activity.