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Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa
Open accessPreprint — published as 10.1038/s41586-021-03402-9 · Paper page
Abstract
Summary: Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.
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“Additionally, K417N, Y453F, S477R, N501Y, and D614G represent circulating variants some of which have been associated with rapidly increasing case numbers14,15,19,33–35.”
From mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (2021) · cites this paper as [19]
In the citing paper
“Recently, viral variants of concern have emerged in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1) that harbor specific mutations in their S proteins that may be associated with increased transmissibility (50–55).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [52]
In the citing paper
“An A701V mutation in S2 is also observed at high frequencies, whereas deletions in residues 242 to 244 as well as R246I and L18F mutations in the NTD are present at lower frequencies (52).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [52]
In the citing paper
“the B.1.351 lineage, which is defined by the D80A (amino acid substitution from aspartic acid to alanine at position 80) and D215G mutations in the NTD; the K417N, E484K, and N501Y mutations in the RBD; and the D614G mutation in S1 (52, 56).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [52]
In the citing paper
“By contrast, the NTD region itself, which appears to tolerate antigenic variation in SARS-CoV-2 and other coronaviruses (50, 52, 55, 85), does not appear to be the target of cross-nAbs elicited by infection or vaccination.”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [52]
In the citing paper
“However, it should be noted that further mutations in spike protein observed in other novel lineages7, 8 appear to be driven by escape of the virus from the neutralising activity of public antibodies,40, 41 indicating that prevention of transmission might be temporary as the virus adapts to natural or vaccine-induced immunity.”
In the citing paper
“The B.1.351 variant is characterized by three deleterious mutations at key antigenic sites in the RBD, including N501Y, K417N, and E484K, with the latter two having particular functional impact.”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [15]
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“the virus must be continuously updated owing to the occurrence of several virus mutations designed to adapt to the environment [45,47-50].”
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“Its mutations include three changes in the receptor-binding domain (RBD), namely N501Y, K417N, and E484K (Tegally et al., 2020).”
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“A trial performed in South Africa showed that AstraZeneca vaccine is significantly less efficient against mild to moderate COVID-19 caused by B.1.351 variants [56].”
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“several mutations in the S glycoprotein like ∆69/70, ∆147, N501y, A570D, P681H, T716I, S982A, D1118H in UK variant; D80A, D251G, ∆241/242/243, K417N, E484K, N501Y, A701V in South African variant; L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y, T1027I in Brazilian variant; and S13I, W152C, L452Q in Californ…”
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Metadata
- Authors
- Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., Mlisana, K., von Gottberg, A., Walaza, S., Allam, M., Ismail, A., Mohale, T., Glass, A. J., Engelbrecht, S., Van Zyl, G., Preiser, W., Petruccione, F., Sigal, A., Hardie, D., Marais, G., Hsiao, M., Korsman, S., Davies, M.-A., Tyers, L., Mudau, I., York, D., Maslo, C., Goedhals, D., Abrahams, S., Laguda-Akingba, O., Alisoltani-Dehkordi, A., Godzik, A., Wibmer, C. K., Sewell, B. T., Lourenço, J., Alcantara, L. C. J., Pond, S. L. K., Weaver, S., Martin, D., Lessells, R. J., Bhiman, J. N., Williamson, C., & de Oliveira, T.
- Affiliations
- University of KwaZulu-Natal (ZA)
- Universidade Federal de Minas Gerais (BR)
- University of Cape Town (ZA)
- National Health Laboratory Service (ZA)
- University of the Witwatersrand (ZA)
- Stellenbosch University (ZA)
- National Institute for Theoretical Physics (ZA)
- Max Planck Institute for Infection Biology (DE)
- Molecular Diagnostics Services (ZA)
- University of the Free State (ZA)
- Walter Sisulu University (ZA)
- University of California, Riverside (US)
- University of Oxford (GB)
- Temple University (US)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- ORCID
- Tegally, Houriiyah
- Wilkinson, Eduan
- Giovanetti, Marta
- Iranzadeh, Arash
- Fonseca, Vagner
- Giandhari, Jennifer
- Pillay, Sureshnee
- Msomi, Nokukhanya
- Mlisana, Koleka
- Walaza, Sibongile
- Allam, Mushal
- Ismail, Arshad
- Mohale, Thabo
- Glass, Allison J
- Engelbrecht, Susan
- Preiser, Wolfgang
- Petruccione, Francesco
- Sigal, Alex
- Hardie, Diana
- Marais, Gert
- Hsiao, Marvin
- Korsman, Stephen
- Davies, Mary-Ann
- Tyers, Lynn
- Maslo, Caroline
- Goedhals, Dominique
- Laguda-Akingba, Oluwakemi
- Godzik, Adam
- Wibmer, Constantinos Kurt
- Sewell, Bryan Trevor
- Lourenço, José
- Pond, Sergei L Kosakovsky
- Weaver, Steven
- Martin, Darren
- Lessells, Richard J
- Bhiman, Jinal N
- Williamson, Carolyn
- de Oliveira, Tulio
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2020-12-22
- Volume
- 592
- Issue
- 7854
- Pages
- 438-443
- ISSN
- 0028-0836 (ISSN-L)
- OpenAlex
- W3135383916
- Cited by
- 2,535
- References
- 39
- Citations by year
- 2026: 52 · 2025: 105 · 2024: 167 · 2023: 308 · 2022: 738 · 2021: 1136 · 2020: 13
- FWCI
- 185.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Department of Science and Innovation, South Africa
- South African Medical Research Council
- Medical Research Council
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, Beta variant, variants of concern, spike protein mutations, receptor binding domain, K417N, E484K, N501Y, viral evolution, transmissibility, immune evasion, South Africa, Eastern Cape, Nelson Mandela Bay
- MeSH terms
- COVID-19, SARS-CoV-2, DNA Mutational Analysis, Humans, Models, Molecular, Mutation, Phylogeny, Selection, Genetic, South Africa, Time Factors, Evolution, Molecular, Genetic Fitness, Immune Evasion, Phylogeography, Spike Glycoprotein, Coronavirus
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