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One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil. [ABSTRACT FROM AUTHOR]

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141–144, ∆211, and ∆256–258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern. [ABSTRACT FROM AUTHOR]

The six Brazilian genomes, as analysed by the Nexclade algorithm (https://clades.nextstrain.org/), exhibited almost all the lineage's 30 synapomorphies.1 The N gene T366I substitution was not present in three SP sequences (EPI ISL 2674368, EPI ISL 1966094 and EPI ISL 1445272). Keywords: SARS-CoV-2; Lambda; South America; Brazil; C.37 EN SARS-CoV-2 Lambda South America Brazil C.37 1 3 3 01/05/22 20211201 NES 211201 The SARS-CoV-2 variant assigned to PangoLineage C.37 was first reported in late December 2020 in Peru and by April 2021 was responsible for 97% of new infections in that country.1 It is currently expanding in Chile and Argentina, and there is evidence of onward transmission in Colombia, Ecuador, Mexico, the USA, Germany and Israel.2 C.37 presents 30 molecular signatures, seven nonsynonymous substitutions (G75V, T76I, R246N, L452Q, F490S, D614G, T859N) and a deleted region ( 247-253) in the Spike protein.1 Another deleted region is found in the ORF1a gene ( 3675-3677) also present in variants of concern Alpha, Beta and Gamma.1 Due to genomic characteristics and epidemiological relevance, on 15 June 2021, WHO designated C.37 as Variant of Interest (VOI) Lambda.2 SP , sp SP . sp 3 Until 26 July 2021, six cases of C.37 were notified in Brazil, two in the southern state of Rio Grande do Sul (RS) and four in the southeastern state of São Paulo (SP). SARS-CoV-2, Lambda, South America, Brazil, C.37. [Extracted from the article]