A5048226033- Hepatitis C virus research
- Evolution and Genetic Dynamics
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Plant Virus Research Studies
- Bacteriophages and microbial interactions
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Animal Virus Infections Studies
- Mathematical and Theoretical Epidemiology and Ecology Models
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Viral Infections and Vectors
- Microbial Metabolic Engineering and Bioproduction
- CRISPR and Genetic Engineering
- Viral gastroenteritis research and epidemiology
- Epigenetics and DNA Methylation
- Innovative Microfluidic and Catalytic Techniques Innovation
- COVID-19 epidemiological studies
- Mitochondrial Function and Pathology
- Infectious Encephalopathies and Encephalitis
- Zoonotic diseases and public health
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
Centro de Biología Molecular Severo Ochoa
2018-2024
Consejo Superior de Investigaciones Científicas
2018-2024
Universidad Autónoma de Madrid
2018-2024
Instituto de Salud Carlos III
2021-2023
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2021-2023
Eulji University
2022
University of Pisa
2019
Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but events intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval Madrid (Spain), at time transition between clades 19 and 20. SOMs have been trained with repertoire present mutant spectra nsp12- spike (S)-coding regions. Each...
There is a need for effective anti-COVID-19 treatments, mainly individuals at risk of severe disease such as the elderly and immunosuppressed. Drug repositioning has proved in identifying drugs that can find new application control coronavirus disease, particular COVID-19. The purpose present study was to synergistic antiviral combinations COVID-19 based on lethal mutagenesis.
Populations of RNA viruses are composed complex and dynamic mixtures variant genomes that termed mutant spectra or clouds. This applies also to SARS-CoV-2, mutations detected at low frequency in an infected individual can be dominant (represented the consensus sequence) subsequent variants interest concern. Here we briefly review main conclusions our work on spectrum characterization hepatitis C virus (HCV) SARS-CoV-2 nucleotide amino acid levels address following two new questions derived...
Hepatitis C virus (HCV) core is a highly conserved and multifunctional protein that forms the viral capsid, making it an attractive target for HCV detection inhibition. Aptamers are in vitro selected, single-stranded nucleic acids (RNA or ssDNA) with growing applicability diagnostics therapy. We have carried out DNA RNA selection against six different variants of protein: two versions full-length genotype 1, hydrophilic domain genotypes 1 to 4. The aptamer populations obtained were analyzed...
Replication of SARS-CoV-2 in the human population is defined by distributions mutants that are present at different frequencies within infected host and can be detected ultra-deep sequencing techniques. In this study, we examined mutant spectra amplicons from spike-coding (S-coding) region 5 nasopharyngeal isolates derived patients with vaccine breakthrough. Interestingly, all became Alpha variant, but amino acid substitutions correspond to Delta Plus, Iota, Omicron variants were resident...
Mutant spectra of RNA viruses are important to understand viral pathogenesis and response selective pressures. There is a need characterize the complexity mutant in coronaviruses sampled from infected patients. In particular, possible relationship between SARS-CoV-2 spectrum disease associations has not been established. present study, we report an ultradeep sequencing (UDS) analysis amplicons nsp12 (polymerase)- spike (S)-coding regions 30 nasopharyngeal isolates (diagnostic samples) first...
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 SARS-CoV-2 replicating in absence or presence indicated increase number mutations, but not deletions, modification diversity indices, expected from activity.
Previous studies documented that long-term hepatitis C virus (HCV) replication in human hepatoma Huh-7.5 cells resulted viral fitness gain, expansion of the mutant spectrum, and several phenotypic alterations. In present work, we show mutational waves (changes frequency individual mutations) occurred continuously became more prominent as gained fitness. They were accompanied by an increasing proportion heterogeneous genomic sites affected 1 position initial HCV population 19 69 positions at...
Despite the high virological response rates achieved with current directly acting antiviral agents (DAAs) against hepatitis C virus (HCV), around 2% to 5% of treated patients do not achieve a sustained viral response. The identification amino acid substitutions associated treatment failure requires analytical designs, such as subtype-specific ultradeep sequencing (UDS) methods, for HCV characterization and patient management. Using this procedure, we have identified six highly represented...
SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical different clade. Here we use high resolution ultra-deep sequencing to analyze mutant spectra. In 6 out 11 from COVID-19 patients, the spectrum spike (S)-coding region included two more deletions, correspond discordant viral clades. A similar observation is reported for laboratory populations USA-WA1/2020, following cell culture infection in presence remdesivir,...
Introduction Cellular epigenetic modifications occur in the course of viral infections. We previously documented that hepatitis C virus (HCV) infection human hepatoma Huh-7.5 cells results a core protein-mediated decrease Aurora kinase B (AURKB) activity and phosphorylation Serine 10 histone H3 (H3Ser10ph) levels, with an affectation inflammatory pathways. The possible role HCV fitness infection-derived cellular is not known. Methods Here we approach this question using populations display...
Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by excess of mutations acquired during replication the presence mutagenic agent, often nucleotide analogue. One its advantages broad spectrum nature renders strategy potentially effective against emergent RNA viral infections. Here we describe synergistic lethal hepatitis C (HCV) combination favipiravir (T-705) and ribavirin. Synergy has been documented over range analogue concentrations using Chou-Talalay...
The influence of quasispecies dynamics on long-term virus diversification in nature is a largely unexplored question. Specifically, whether intra-host nucleotide and amino acid variation fit the observed consensus sequences or data bank alignments unknown. Genome conservation simulations are used for computational design universal vaccines, therapeutic antibodies pan-genomic antiviral agents. expectation that selection escape mutants will be limited when mutations at conserved residues...
RNA viruses replicate as complex mutant spectra termed viral quasispecies. The frequency of each individual genome in a spectrum depends on its rate generation and relative fitness the replicating population ensemble. advent deep sequencing methodologies allows for first-time quantification haplotype abundances within spectra. There is no information profile resident genomes how landscape evolves when virus replicates controlled cell culture environment. Here, we report construction...
In the course of experiments aimed at deciphering inhibition mechanism mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect nucleoside guanosine (Gua). Here, report that Gua, not other standard nucleosides, inhibits HCV replication human hepatoma cells. Gua did directly inhibit vitro polymerase activity NS5B, but it modified intracellular levels di- tri-phosphates (NDPs NTPs), leading to deficient RNA reduction infectious progeny production....
Abstract The influence of quasispecies dynamics on long-term virus diversification in nature is a largely unexplored question. Specifically, whether intra-host nucleotide and amino acid variation fits observed consensus sequences or data bank alignments unknown. Genome conservation simulations are used for the computational design universal vaccines, therapeutic antibodies pan-genomic antiviral agents. expectation that selection escape mutants will be limited when mutations at conserved...