2026-07-21T14:15:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/190152025-05-05T07:13:22Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16977

00925njm 22002777a 4500 dc Delgado, Soledad author Somovilla, Pilar author Ferrer-Orta, Cristina author Martínez-González, Brenda author Vázquez-Monteagudo, Sergi author Muñoz-Flores, Javier author Soria, Maria Eugenia author García-Crespo, Carlos author de Ávila, Ana Isabel author Durán-Pastor, Antoni author Gadea, Ignacio author Lopez-Galindez, Luis Cecilio author Morán, Federico author Lorenzo-Redondo, Ramon author Verdaguer, Nuria author Perales, Celia author Domingo, Esteban author 2024-03-05 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. Proc Natl Acad Sci USA. 2024 Mar 5;121(10):e2317851121. 10.1073/pnas.2317851121 1091-6490 Proceedings of the National Academy of Sciences of the United States of America 38416684 http://hdl.handle.net/20.500.12105/19015 COVID-19 Clade transition Viral quasispecies Self-organized maps Intrahost evolution Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps