Dataset Information

SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions.

ABSTRACT: Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.

SUBMITTER: Timmers LFSM

PROVIDER: S-EPMC8184806 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions.

Timmers Luis Fernando Saraiva Macedo LFSM Peixoto Julia Vasconcellos JV Ducati Rodrigo Gay RG Bachega José Fernando Ruggiero JFR de Mattos Pereira Leandro L Caceres Rafael Andrade RA Majolo Fernanda F da Silva Guilherme Liberato GL Anton Débora Bublitz DB Dellagostin Odir Antônio OA Henriques João Antônio Pegas JAP Xavier Léder Leal LL Goettert Márcia Inês MI Laufer Stefan S

Scientific reports 20210607 1

Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis broug ...[more]

PMID: 34099808

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Project description:BackgroundP.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies.MethodsThe samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples.ResultsForty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage.ConclusionP.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.

Dataset Information

SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions.

Publications

SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions.

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