Comparative genomics and characterization of SARS-CoV-2 P.1 (Gamma) Variant of Concern (VOC) from Amazonas, Brazil

Abstract

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.

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“…As for the antibody treatment in clinical use, the cocktail consisting of LY-CoV555 (also known as Bamlanivimab) and LY-CoV016 (also known as Etesevimab) has been authorized for emergency use. Previous studies have revealed that the mutations at 484 and 417 positions of the spike are associated with immune evasion 22 and that both Beta and Gamma variants could escape the neutralization of LY-CoV555 (due to E484K) and LY-CoV016 (due to K417N/T). 23 Since the Omicron variant also contains E484A and K417N mutations, it is likely that Omicron would also resist these two antibodies.…”

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“…Is more likely to occur in P.1 (18.2%) [108], but globally the deletion (NSP6:S106/G107/F108del) is more common in this position. According to GISAID (as on 1 September 2021), this deletion is found in 97.21% of the sequences [109].…”

“…Is more likely to occur in P.1 (18.2%) [108], but globally the deletion (NSP6:S106/G107/F108del) is more common in this position. According to GISAID (as on 1 September 2021), this deletion is found in 97.21% of the sequences [109]. Sun et al suggested that this mutation may affect viral shedding and hence transmissibility, thereby altering viral load [110].…”

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