Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in South America

Franco-Muñoz, Carlos; Álvarez-Díaz, Diego A.; Laiton‐Donato, Katherine; Wiesner, Magdalena; Escandón, Patricia; Usme-Ciro, José A.; Franco‐Sierra, Nicolás D.; Flórez-Sánchez, Astrid C.; Gómez-Rangel, Sergio; Rodríguez-Calderon, Luz D.; Barbosa-Ramírez, Juliana; Ospitia-Baez, Erika; Walteros, Diana Marcela; Ospina-Martínez, Martha Lucia; Mercado, Marcela

doi:10.1016/j.meegid.2020.104557

Cited by 29 publications

(31 citation statements)

References 25 publications

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“…South America presents a greater OTU_3 frequency ( Figure 2C ) that was established in April ( Supplementary Figure S5 ). This observation correlates well with studies focused in South America that detect the establishment of D614G mutation at the end of March (mutation presents in OTU_2, OTU_3, OTU_4 and OTU_5) and a high frequency of pangolin lineage B1.1 in Chile and in general in South America that contains the same characteristics mutations that our OTU_3 ( Castillo et al, 2020 ; Franco-Muñoz et al, 2020 ). Unfortunately, few genomes are reported in South America for September, October, and November (24 genomes in total in the three months), hindering a correct analysis of frequencies in these months.…”

Section: Resultssupporting

confidence: 91%

“…Several analyses have been performed to identify SARS-CoV-2 variants around the world, most of them on a particular group of genomes using limited datasets (For example, Castillo et al, 2020 ; Franco-Muñoz et al, 2020 ; Maitra et al, 2020 ; Saha et al, 2020 ). In March 2020, two major lineages were proposed based on position 8,782 and 28,144 using a data set of 103 genomes ( Tang et al, 2020 ) which was followed by a particularly interesting proposal that identified the same major lineages (named A and B) and other sublineages ( Rambaut et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases During the Pandemic

et al. 2021

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Since the identification of SARS-CoV-2, a large number of genomes have been sequenced with unprecedented speed around the world. This marks a unique opportunity to analyze virus spreading and evolution in a worldwide context. Currently, there is not a useful haplotype description to help to track important and globally scattered mutations. Also, differences in the number of sequenced genomes between countries and/or months make it difficult to identify the emergence of haplotypes in regions where few genomes are sequenced but a large number of cases are reported. We propose an approach based on the normalization by COVID-19 cases of relative frequencies of mutations using all the available data to identify major haplotypes. Furthermore, we can use a similar normalization approach to tracking the temporal and geographic distribution of haplotypes in the world. Using 171,461 genomes, we identify five major haplotypes or operational taxonomic units (OTUs) based on nine high-frequency mutations. OTU_3 characterized by mutations R203K and G204R is currently the most frequent haplotype circulating in four of the six continents analyzed (South America, North America, Europe, Asia, Africa, and Oceania). On the other hand, during almost all months analyzed, OTU_5 characterized by the mutation T85I in nsp2 is the most frequent in North America. Recently (since September), OTU_2 has been established as the most frequent in Europe. OTU_1, the ancestor haplotype, is near to extinction showed by its low number of isolations since May. Also, we analyzed whether age, gender, or patient status is more related to a specific OTU. We did not find OTU’s preference for any age group, gender, or patient status. Finally, we discuss structural and functional hypotheses in the most frequently identified mutations, none of those mutations show a clear effect on the transmissibility or pathogenicity.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases During the Pandemic

et al. 2021

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“…High diversity was found among the Venezuelan viral isolates sequenced from the early period of the Venezuelan epidemic. The sequences were similar to the one found in other countries of Latin America, with the predominance of lineage B isolates [ 11 – 14 ].…”

Section: Discussionsupporting

confidence: 76%

SARS-CoV-2 genetic diversity in Venezuela: Predominance of D614G variants and analysis of one outbreak

et al. 2021

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SARS-CoV-2 is the new coronavirus responsible for COVID-19 disease. The first two cases of COVID-19 were detected in Venezuela on March 13, 2020. The aim of this study was the genetic characterization of Venezuelan SARS-CoV-2 isolates. A total of 7 full SARS-CoV-2 genome sequences were obtained by Sanger sequencing, from patients of different regions of Venezuela, mainly from the beginning of the epidemic. Ten out of 11 isolates (6 complete genomes and 4 partial spike genomic regions) belonged to lineage B, bearing the D614G mutation in the Spike protein. Isolates from the first outbreak that occurred in the Margarita Island harbored an in-frame deletion in its sequence, without amino acids 83–85 of the NSP1 of the ORF1. The search for deletions in 48,635 sequences showed that the NSP1 gene exhibit the highest frequency of deletions along the whole genome. Structural analysis suggests a change in the N-terminal domain with the presence of this deletion. In contrast, isolates circulating later in this island lacked the deletion, suggesting new introductions to the island after this first outbreak. In conclusion, a high diversity of SARS-CoV-2 isolates were found circulating in Venezuela, with predominance of the D614G mutation. The first small outbreak in Margarita Island seemed to be associated with a strain carrying a small deletion in the NSP1 protein, but these isolates do not seem to be responsible for the larger outbreak which started in July.

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“…The missense mutation in ORF1ab (L3930F) was reported in other 429 sequences (125 from Brazil) and also in two sequences of lineage B.1.1.248 from the Philippines [60]. Interestingly, the I33F and I292T mutations that were found in ORF6 and N, respectively, have been considered dominant mutations in the SARS-CoV-2 sequences from Brazil [61,62]. The co-occurrence of these mutations represents the signature of Clade 2 (subsequently named B.1.1.33 lineage), which were one of the three most prevalent Brazilian viral lineage groups in the beginning of the pandemic, highly widespread in 16 states from Brazil [12].…”

Section: Discussionmentioning

confidence: 79%

Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil

et al. 2021

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Background Brazil is the third country most affected by Coronavirus disease-2019 (COVID-19), but viral evolution in municipality resolution is still poorly understood in Brazil and it is crucial to understand the epidemiology of viral spread. We aimed to track molecular evolution and spread of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Esteio (Southern Brazil) using phylogenetics and phylodynamics inferences from 21 new genomes in global and regional context. Importantly, the case fatality rate (CFR) in Esteio (3.26%) is slightly higher compared to the Rio Grande do Sul (RS) state (2.56%) and the entire Brazil (2.74%). Results We provided a comprehensive view of mutations from a representative sampling from May to October 2020, highlighting two frequent mutations in spike glycoprotein (D614G and V1176F), an emergent mutation (E484K) in spike Receptor Binding Domain (RBD) characteristic of the B.1.351 and P.1 lineages, and the adjacent replacement of 2 amino acids in Nucleocapsid phosphoprotein (R203K and G204R). E484K was found in two genomes from mid-October, which is the earliest description of this mutation in Southern Brazil. Lineages containing this substitution must be subject of intense surveillance due to its association with immune evasion. We also found two epidemiologically-related clusters, including one from patients of the same neighborhood. Phylogenetics and phylodynamics analysis demonstrates multiple introductions of the Brazilian most prevalent lineages (B.1.1.33 and B.1.1.248) and the establishment of Brazilian lineages ignited from the Southeast to other Brazilian regions. Conclusions Our data show the value of correlating clinical, epidemiological and genomic information for the understanding of viral evolution and its spatial distribution over time. This is of paramount importance to better inform policy making strategies to fight COVID-19.

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Substitutions in Spike and Nucleocapsid proteins of SARS-CoV-2 circulating in South America

Cited by 29 publications

References 25 publications

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases During the Pandemic

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases During the Pandemic

SARS-CoV-2 genetic diversity in Venezuela: Predominance of D614G variants and analysis of one outbreak

Genomic epidemiology of SARS-CoV-2 in Esteio, Rio Grande do Sul, Brazil

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