A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Dl, Bugembe; Phan, My; Ssewanyana, Isaac; Semanda, Patrick; Nansumba, Hellen; Dhaala, Beatrice; Nabadda, Susan; Án, O’Toole; Rambaut, Andrew; Kaleebu, Pontiano; Cotten, Matthew

doi:10.1101/2021.02.08.21251393

Cited by 41 publications

(63 citation statements)

References 39 publications

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“…At least two emergent lineages of concern, B.1.1.7 (501Y.V1), and a newer variant whose prevalence is on the rise in Uganda both contain amino acid substitutions affecting the first position of the polybasic cleavage site, S:P681H and S:P681R, respectively (Andrew Rambaut, Nick Loman, Oliver Pybus, Wendy Barclay, Jeff Barrett, Alesandro Carabelli, Tom Connor, Tom Peacock, David L Robertson, Erik Volz, COVID- 19 Genomics Consortium UK (CoG-UK), 2020; Lule Bugembe et al ., 2021). The polybasic site strongly impacts viral replication in culture and as well as pathogenesis in animal models (Hoffmann, Kleine-Weber and Pöhlmann, 2020; Johnson et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

Hodcroft

Domman

Snyder³

et al. 2021

Preprint

122

116

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.

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Section: Discussionmentioning

confidence: 99%

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

Hodcroft

Domman

Snyder³

et al. 2021

Preprint

122

116

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“…9, Figure 6, detailed in Table 1) is only second to the VOCs B.1.1.7, B.1.351 and P.1, and slightly lower than the emerging lineage P.3. Curiously, this rate of molecular evolution appears to be much higher than the VOCs B.1.427 and B.1.429 [44], and superior to that of other recently described emerging lineage A variants, such as A.23.1 and A.27 [12]. The total number of substitutions/insertions/deletions found in B.1.214.2, albeit slightly inferior to A.2.5 (i.e.…”

Section: Resultsmentioning

confidence: 68%

“…A.2.5 belongs to one of the very few surviving children lineages of the ancestral lineage A, which, after several months of limited global spread, have recently led to a few major clusters of infections. Such events, that occurred for example in Uganda (A.23.1) [12] and, most likely, also in Tanzania (A.VOI.V2) [12], are characterized, like in the case of A.2.5, by the acquisition of several spike mutations, often shared by other VOCs and VOIs. 2 is, by far, the most widespread (Figure 5), with Belgium being the leading county in terms of genome counts.…”

Section: Resultsmentioning

confidence: 99%

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

Gerdol

2021

Preprint

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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.

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“…Interestingly, S477 has been identified as the most flexible amino acid within the RBM and with the largest number of mutations (Singh et al 2021), which might be stabilized by mutation T478K. A case exemplifying a similar scenario in which physically close mutations contribute towards an analogous structural solution has been suggested for the Spike protein mutation Q613H, recently suggested to take a similar role of the well-studied and broadly distributed D614G in an emerging lineage, A.23.1, in Uganda, Africa (Bugembe et al 2021).…”

Section: Discussionmentioning

confidence: 83%

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4, B.1.1.222 or B.1.1.519 and B.1.243 with mutations in the Spike protein and the Nucleocapsid

Barona‐Gómez

Delaye

Diaz-Valenzuela

et al. 2021

Preprint

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Understanding the evolution of SARS-CoV-2 virus in various regions of the world during the Covid19 pandemic is of the utmost importance to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. Our RT-qPCR screening and phylogenomics directed a sequence/structure analysis of the Spike glycoprotein, revealing mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show mutations in the N-terminal domain (i.e., R190M), in the receptor-binding motif (i.e., T478K, E484K), within the S1-S2 subdomains (i.e., P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the postulated variants of interest (VOIs) 20B/478K.V1 and P.3. Moreover, the population patterns of Single Nucleotide Variants (SNVs) from symptomatic and asymptomatic carriers sampled with a self-sampling scheme, revealed a bimodal distribution of polymorphisms in all three sampled localities from central Mexico, and confirmed the presence of several fixed variants, mostly from the 241T-3037T-14408T-23403G haplotype common in Asia. Despite gene flow among Mexican localities, we found differences in both the allelic frequencies among localities and the allelic imbalance of the mutation S194L of the nucleocapsid protein between symptomatic and asymptomatic carriers. Our results highlight the dual role of Spike and Nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage in Mexico.

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A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic

Cited by 41 publications

References 39 publications

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677

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

Phylogenomics and population genomics of SARS-CoV-2 in Mexico during the pre-vaccination stage reveals variants of interest B.1.1.28.4, B.1.1.222 or B.1.1.519 and B.1.243 with mutations in the Spike protein and the Nucleocapsid

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