%0 Journal Article
%T SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
%A Martínez-González B
%A Soria ME
%A Mínguez P
%A Lorenzo-Redondo R
%A Salar-Vidal L
%A López-García A
%A Esteban-Muñoz M
%A Durán-Pastor A
%A Somovilla P
%A García-Crespo C
%A de Ávila AI
%A Gómez J
%A Esteban J
%A Fernández-Roblas R
%A Gadea I
%A Domingo E
%A Perales C
%J Front Microbiol
%V 15
%N 0
%D 2024
%M 38559344
%F 6.064
%R 10.3389/fmicb.2024.1358258
%X <B>UNASSIGNED: </B>SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.<BR><B>UNASSIGNED: </B>Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.<BR><B>UNASSIGNED: </B>In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.<BR><B>UNASSIGNED: </B>We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.