PreprintCited by 2,535SARS-CoV-2 and COVID-19 ResearchCOVID-19 epidemiological studiesSARS-CoV-2 detection and testing

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 access
Tegally, Houriiyah, Wilkinson, Eduan, Giovanetti, Marta, Iranzadeh, Arash, Fonseca, Vagner, Giandhari, Jennifer, Doolabh, Deelan, Pillay, Sureshnee +39 more·2020·Nature

Preprint — 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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Crossref · 10.1101/2020.12.21.20248640

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  • The panel also included circulating variant residues K417N, Y453F, S477R, N501Y, and D614G, some linked to rapidly rising case counts.

    “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.”
  • 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.

    “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).”
  • An A701V mutation in S2 is also observed at high frequencies in B.1.351, whereas deletions in residues 242 to 244 as well as R246I and L18F mutations in the NTD are present at lower frequencies.

    “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).”
  • The B.1.351 lineage is defined by the D80A and D215G mutations in the NTD; the K417N, E484K, and N501Y mutations in the RBD; and the D614G mutation in S1.

    “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).”
  • The NTD region itself does not appear to be the target of cross-nAbs elicited by infection or vaccination.

    “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.”

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Research works printed but not linked: 1

  1. Hsiao M, Davies MA, Kalk E, et al. SARS-CoV-2 seroprevalence in the Cape Town Metropolitan sub-districts after the peak of infections. NICD COVID-19 Special Public Health Surveillance Bulletin. 2020;18:1-9.

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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)
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 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
185.77
Type
journal article
Language
en
Open access
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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