The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Martin, Darren P.; Weaver, Steven; Tegally, Houryiah; San, Emmanuel James; Shank, Stephen D; Wilkinson, Eduan; Lucaci, Alexander G; Giandhari, Jennifer; Naidoo, Sureshnee; Pillay, Yeshnee; Singh, Lavanya; Lessells, Richard; Gupta, Ravindra; Wertheim, Joel O.; Nekturenko, Anton; Murrell, Ben; Harkins, Gordon William; Lemey, Philippe; MacLean, Oscar A; Robertson, David L.; Oliveira, Túlio de; Pond, Sergei L. Kosakovsky

doi:10.1101/2021.02.23.21252268

Cited by 92 publications

(106 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The onset date of VOI N.9 here estimated around mid-August roughly coincides with the estimated timing of emergence of the VOI P.2 in late-July 6 and shortly precede the detection of a major global shift in the SARS-CoV-2 fitness landscape after October 2020 [20]. These findings indicate that 484K variants probably arose simultaneously in the two most prevalent viral lineages circulating in Brazil around July-August, but may have only acquired some fitness advantages, which accelerated its dissemination, after October 2020.…”

Section: Discussionsupporting

confidence: 72%

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Resende

Gräf

Paixão

et al. 2021

Viruses

View full text Add to dashboard Cite

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

show abstract

Section: Discussionsupporting

confidence: 72%

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Resende

Gräf

Paixão

et al. 2021

Viruses

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint this version posted March 25, 2021. ; https://doi.org/10.1101/2021.03.21.21253418 doi: medRxiv preprint Convergent mutations seem to play an essential role in the evolutionary dynamics of SARS-CoV-2. Intense selective pressure from the immune system against prolonged infections may promote intrahost variants with higher adaptive value [12,[35][36][37][38][39]. Previous studies have shown that both N501Y and E484K have independently emerged in patients with persistent infection [35,40].…”

Section: Discussionmentioning

confidence: 99%

Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil

Lamarca

Almeida

Francisco

et al. 2021

Preprint

View full text Add to dashboard Cite

The sharp increase of COVID-19 cases in late 2020 has made Brazil the new epicenter of the ongoing SARS-CoV-2 pandemic. Novel SARS-CoV-2 lineages P.1 and P.2, first identified respectively in Manaus and Rio de Janeiro, have been associated with potentially higher transmission rates and antibody neutralization escape. In this study, we performed a whole-genome sequencing of 185 samples isolated from three out of the five Brazilian regions, including Amazonas (North region), Rio Grande do Norte, Paraiba and Bahia (Northeast region), and Rio de Janeiro (Southeast region) aiming to identify SARS-CoV-2 mutations that could be involved in the surge of COVID19 cases in Brazil. Here, we showed a widespread dispersion of P.1 and P.2 across Brazilian regions. Except for Manaus, P.2 was the predominant lineage identified country-wise. P.2 lineage was estimated to have originated in February, 2020 and has diverged into new clades. Interstate transmission of P.2 was detected since March, but reached its peak in December, 2020 and January, 2021. Transmission of P.1 was also high in December. P.1 origin was inferred to have happened in August 2020. We also confirmed the presence of the variant under investigation (VUI) NP13L recently described in the southernmost region of Brazil to have spread across the Northeastern states. P.1, P.2 and NP13L are descended from the ancient B.1.1.28 strain, although during the first phase of the pandemic in Brazil presence of B.1.1.33 strain was also reported. Here, for the first time, we investigate the possible occurrence of a new variant of concern descending from B.1.1.33 that also carries the E484K mutation. Indeed, the recurrent report of many novel SARS-CoV-2 genetic variants in Brazil could be due to the absence of effective control measures resulting in high SARS-CoV2 transmission rates. Altogether, our findings provided a landscape of the critical state of SARS-CoV-2 across Brazil and confirm the need to sustain continuous sequencing of the SARS-CoV-2 isolates worldwide in order to early identify novel variants of concern and to monitor for vaccine effectiveness.

show abstract

“…Similarly, additional fourplex master mixtures contained sets of primers and probes to determine whether a SARS-CoV-2 isolate belongs to the L or S strain (Tang et al 2020). Other examples of fourplex reactions included primer-probe sets to identify the SNP found in Spike gene at position 23,063 (thymine instead of adenine) that results in an amino acid substitution N501Y that triggers a stronger interaction of the Spike receptor-binding domain with the human cell-surface receptor angiotensinconverting enzyme 2 (ACE2) (Leung et al 2021;Martin et al 2021). This multiplex approach could facilitate tracking of SARS-CoV-2 variants that carry mutations.…”

Section: Limits Of Detection (Lod)mentioning

confidence: 99%

“…Since the beginning of the COVID-19 pandemic, several studies have reported genomic sequence variations of SARS-CoV-2 isolates (Leung et al 2021;Martin et al 2021;Rondinone et al 2021;Tegally et al 2021a;Tegally et al 2021b). Among these genetic variations, a single nucleotide polymorphism (SNP) found at position 8,782 (in orf1ab; C instead of T) of SARS-CoV-2 genomic sequence is a hallmark of the L strain (Tang et al 2020), whereas the unaltered nucleotide is found at the same position in the S strain.…”

Section: Introductionmentioning

confidence: 99%

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays

Durand

Thibault

Lévesque

et al. 2021

Preprint

View full text Add to dashboard Cite

The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 (COVID-19). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes. Furthermore, a newly developed primer-probe set targeted human beta-2 microglobulin (B2M) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected less than or equal to 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.

show abstract

The emergence and ongoing convergent evolution of the N501Y lineages coincides with a major global shift in the SARS-CoV-2 selective landscape

Cited by 92 publications

References 96 publications

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

A Potential SARS-CoV-2 Variant of Interest (VOI) Harboring Mutation E484K in the Spike Protein Was Identified within Lineage B.1.1.33 Circulating in Brazil

Genomic surveillance of SARS-CoV-2 tracks early interstate transmission of P.1 lineage and diversification within P.2 clade in Brazil

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays

Contact Info

Product

Resources

About