The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein

Resende, Paola Cristina; Naveca, Felipe Gomes; Lins, Roberto D.; Dezordi, Filipe Zimmer; Ferraz, Matheus; Moreira, Emerson G.; Coêlho, Danilo F.; Motta, Fernando Couto; Paixão, Ariane Gomes; Appolinario, Luciana; Lopes, Renata Serrano; Mendonça, Ana Carolina da Fonseca; Rocha, Alice Sampaio Barreto da; Nascimento, Valdinete Alves do; Souza, Victor Costa de; Silva, George; Nascimento, Fernanda; Lima-Neto, Lidio Gonçalves; Silva, Fabiano Vieira da; Riediger, Irina Nastassja; Debur, Maria do Carmo; Leite, Anderson Brandão; Mattos, Tirza; Costa, Cristiano Fernandes da; Pereira, Felicidade Mota; Santos, Cliomar Alves dos; Rovaris, Darcita Büerger; Fernandes, Sandra Bianchini; Abbud, Adriano; Sacchi, Cláudio Tavares; Khouri, Ricardo; Bernardes, André Felipe Leal; Delatorre, Edson; Gräf, Tiago; Siqueira, Marilda Mendonça; Bello, Gonzalo; Wallau, Gabriel Luz

doi:10.1101/2021.03.19.21253946

Cited by 20 publications

(28 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This model is consistent with a recent study that revealed a major change in selective pressures acting on SARS-CoV-2 variants circulating worldwide after October 2020, coinciding with the simultaneous expansion of different VOCs with convergent S mutations 22 . This model is also consistent with the ongoing evolution of the VOC P.1 in Brazil revealed by the recurrent acquisition of indels in the NTD of the S protein 4 .…”

Section: Resultssupporting

confidence: 88%

“…Maximum likelihood phylogenetic analyses SARS-CoV-2 P.1-related sequences here obtained were aligned with high quality (<5% of N) and complete (>29 kb) sequences that were available in the EpiCoV database in the GISAID (https://www.gisaid.org/) on March 31 st , 2021 and belongs to three different clades: 1) B.1.1.28 sequences from Amazonas state, 2) P.1 sequences, and 3) previously described P.1-like sequences 1,4 . This dataset was then aligned using MAFFT v7.475 7 and subjected to maximum likelihood (ML) phylogenetic analysis using IQ-TREE v2.1.2 8 under the GTR+F+R4 nucleotide substitution model, as selected by the ModelFinder application 9 .…”

Section: Sars-cov-2 Whole-genome Sequencingmentioning

confidence: 99%

“…The most accepted hypothesis to explain such a high number of lineage-de ning mutations is that VOCs result from selective pressures and adaptation of the virus during prolonged individual infections and subsequent transmission 3 . This hypothesis, however, was challenged by the early discovery of four P.1like genomes, most of them sampled in the capital city of Amazonas state, that branched as a sister monophyletic clade concerning lineage P.1 1,4 . The P.1-like clade also accumulated an unusually high number of genetic changes, including several P.1 lineage-de ning mutations in the S (L18F, P26S, D138Y, K417T, E484K, N501Y), NSP3 (K977Q), and N (P80R) proteins and unique mutations in the NSP2 (K456R), NSP3 (T1189I), NSP6 (V149A), NSP13 (S74L), S (ins214 and D1139H) and NS8 (K2stop) proteins.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern

Gräf

Bello

Venas

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

One of the most remarkable features of the SARS-CoV-2 Variants of Concern (VOC) is the unusually large number of mutations they carry. 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 described a new SARS-CoV-2 lineage provisionally designated as P.1-like-II that, as well as the previously described lineage P.1-like-I, shares several lineage-defining mutations with the VOC P.1 circulating in Brazil. Reconstructions of P.1 ancestor sequences demonstrate that the entire constellation of mutations that define the VOC P.1 did not accumulate within a single long-term infected individual, but was acquired by sequential addition during interhost transmissions. Our evolutionary analyses further estimate that P.1-ancestors strains carrying half of the P.1-lineage-defining mutations, including those at the receptor-binding domain of the Spike protein, circulated cryptically in the Amazonas state since August 2020. This evolutionary pattern is consistent with the hypothesis that partial human population immunity acquired from natural SARS-CoV-2 infections during the first half of 2020 might have been the major driving force behind natural selection that allowed VOCs' emergence and worldwide spread. These findings also support a long lag-time between the emergence of variants with key mutations of concern and expansion of the VOC P.1 in Brazil.

show abstract

Section: Resultssupporting

confidence: 88%

Section: Sars-cov-2 Whole-genome Sequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern

Gräf

Bello

Venas

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, S:ins214ANRN was found in four viral genomes belonging to the P.1 lineage, sequenced in Manaus (Amazonas, Brazil) between December 2020 and January 2021. As reported in a previous work [48], the four genomes belong to a monophyletic P.1-like clade that appears to be basal to P.1, which suggests that limited transmission in the community might have been present at the time of sampling. P.1 is currently considered one of the major VOCs and its worldwide prevalence is being constantly monitored due to the combination of three key RBD mutations (K417T, E484K and N501Y), which may jeopardize the efficiency of some vaccines by promoting antibody escape [25,49].…”

Section: Presence Of a Recurrent Insertion Region (Rir1) In The N-terminal Domain Of Sars-cov-2 Spike Proteinsupporting

confidence: 76%

Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

Gerdol

2021

Preprint

View full text Add to dashboard Cite

Tracking the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through genomic surveillance programs is undoubtedly one of the key priorities in the current pandemic situation. Although the genome of SARS-CoV-2 acquires mutations at a slower rate compared with other RNA viruses, evolutionary pressures derived from the widespread circulation of SARS-CoV-2 in the human population have progressively favored the global emergence though natural selection of several variants of concern that carry multiple non-synonymous mutations in the spike glycoprotein. Such mutations are often placed in key sites within major antibody epitopes and may therefore confer resistance to neutralizing antibodies, leading to partial immune escape, or otherwise compensate minor infectivity deficits associated with other mutations. As previously shown by other authors, several emerging variants carry recurrent deletion regions (RDRs) that display a partial overlap with antibody epitopes located in the spike N-terminal domain. Comparatively, very little attention has been directed towards spike insertion mutations, which often go unnoticed due to the use of insertion-unaware bioinformatics analysis pipelines. This manuscript describe a single recurrent insertion region (RIR1) in the N-terminal domain of SARS-CoV-2 spike protein, characterized by the independent acquisition of 3-4 additional codons between Arg214 and Asp215 in different viral lineages. Even though RIR1 is unlikely to confer antibody escape, its progressive increase in frequency and its association with two distinct emerging lineages (A.2.5 and B.1.214.2) warrant further investigation concerning its effects on spike structure and viral infectivity.

show abstract

“…However, the identification-in our study and during subsequent surveillance conducted in Manaus between December 2020 and January 2021 (ref. 17 )-of P.1-like viruses that harbor several of the P.1 lineage-defining mutations indicates that P.1 mutations did not accumulate in a single, long-term infection but were acquired in sequential steps as observed in the VOC B.1.351 (ref. 18 ).…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence

Naveca

Nascimento

Souza

et al. 2021

Nat Med

Self Cite

342

302

View full text Add to dashboard Cite

mazonas state reported the first confirmed SARS-CoV-2 case in Manaus, the state capital, in March 2020 in a traveler returning from Europe 1 . By late February 2021, >306,000 laboratory-confirmed cases and more than 10,400 deaths in Amazonas had been reported 2 . The COVID-19 epidemic in Amazonas is, at the time of writing, characterized by two exponentially growing curves of cases (Fig. 1a). Epidemiological data from surveillance of severe acute respiratory illness (SARI) and burials indicate that the first wave of the epidemic started in March 2020 and peaked around early May 2020, when the number of cases dropped and then remained roughly stable from June to November 2020. However, in mid-December the number of cases started to grow exponentially, establishing the second wave of the epidemic.A new SARS-CoV-2 VOC, designated P.1 and also knowns as N501Y.V3, recently emerged in Manaus. Lineage P.1 was first detected in four travelers returning to Japan from Amazonas state on 2 January 2021 (ref. 3 ) and was soon recognized as an emergent lineage in Manaus 4 . The VOC P.1 harbors 21 lineage-defining mutations, including ten in the Spike protein (L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y and T1027I). The emergence of P.1 was touted as one of the putative causes of the second wave of COVID-19 in Manaus 5 . However, the precise relationship between circulating SARS-CoV-2 variants and epidemic dynamics in Amazonas remains unclear due to the paucity of viral sequences sampled in this Brazilian state before December 2020. Results Evidence of successive SARS-CoV-2 lineage replacements in Amazonas.To acquire a more in-depth understanding of the genetic diversity of SARS-CoV-2 variants circulating in Amazonas state since the early epidemic, we generated 250 SARS-CoV-2 high-quality, whole-genome sequences from individuals living in 25 municipalities, between 16 March 2020 and 13 January 2021 (Fig. 1a,b). Viral sequences were generated at FIOCRUZ Amazônia, which is part of both the Amazonas state health genomics network (REGESAM) and the consortium FIOCRUZ COVID-19 Genomics Surveillance Network of the Brazilian Ministry of Health (http:// www.genomahcov.fiocruz.br/). Our genomic survey revealed that most sequences were classified into five lineages:

show abstract

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the Spike protein

Cited by 20 publications

References 53 publications

Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern

Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern

Emergence of a recurrent insertion in the N-terminal domain of the SARS-CoV-2 spike glycoprotein

COVID-19 in Amazonas, Brazil, was driven by the persistence of endemic lineages and P.1 emergence

Contact Info

Product

Resources

About