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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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Virus Corona (SARS-CoV-2) penyebab COVID-19 kini telah bermutasi
Parwanto, E. (2021) · Jurnal Biomedika dan Kesehatan · doi:10.18051/jbiomedkes.2021.v4.47-49 · Cited by 24
Chrysostomou, A. C., Vrancken, B., Koumbaris, G., Themistokleous, G., Aristokleous, A., Masia, C., Eleftheriou, C., Iοannou, C., Stylianou, D. C., Ioannides, M., et al. (2021) · Viruses · doi:10.3390/v13061098 · Cited by 15
Galindo, R. A. R., Chow, H., & Rongkavilit, C. (2021) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2021.05.004 · Cited by 24
Muir, L., Jaffer, A., Rees-Spear, C., Gopalan, V., Chang, F. Y., Fernando, R., Vaitkute, G., Roustan, C., Rosa, A., Earl, C. P., et al. (2021) · Kidney International Reports · doi:10.1016/j.ekir.2021.03.902 · Cited by 15
Phylogenomic Evidence of Reinfection and Persistence of SARS-CoV-2: First Report from Colombia
Ramírez, J. D., Muñoz, M., Ballesteros, N., Patiño, L. H., Castañeda, S., Rincón, C. A., Méndez, C., Oliveros, C., Perez, J., Márquez, E. K., et al. (2021) · Vaccines · doi:10.3390/vaccines9030282 · Cited by 16
A Complementary Union of SARS-CoV2 Natural and Vaccine Induced Immune Responses
Torresi, J., Edeling, M. A., Nolan, T. M., & Godfrey, D. I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.914167 · Cited by 15
“The most prevalent circulating variants carry combinations of changes within the S1, not just RBD and have included Alpha (83), Beta (84), Epsilon (1, 85), Delta (86) and most recently Omicron and its sublineages (18) which are associated with greater transmission and disease severity (1, 85, 87–89) (Figure 3).”
BackgroundA comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort studyPreprint
Anscombe, C., Lissauer, S., Thole, H., Rylance, J., Dula, D., Menyere, M., Kutambe, B., van der Veer, C., Phiri, T., Banda, N. P., et al. (2022) · medRxiv · doi:10.1101/2022.02.17.22269742 · Cited by 15
“use of genomic surveillance to inform public health strategy has been a defining feature of the 79 pandemic [8,9].”
BackgroundAdhikari, P., Jawad, B., Rao, P. R., Podgornik, R., & Ching, W. Y. (2022) · Viruses · doi:10.3390/v14030465 · Cited by 14
Bollen, N., Artesi, M., Durkin, K., Hong, S. L., Potter, B. I., Boujemla, B., Vanmechelen, B., Martí‐Carreras, J., Wawina-Bokalanga, T., Meex, C., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-97667-9 · Cited by 18
Hartard, C., Berger, S., Josse, T., Schvoerer, É., & Jeulin, H. (2021) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2021-0569 · Cited by 19
“V2 [6] and the P80R mutation found in 20J/ 501Y.”
BackgroundInfluentialUp State of the SARS-COV-2 Spike Homotrimer Favors an Increased Virulence for New Variants
Giron, C. C., Laaksonen, A., & da Silva, F. L. B. (2021) · Frontiers in Medical Technology · doi:10.3389/fmedt.2021.694347 · Cited by 25
“For example, the mutation E484K presented at least in three new variants (B1.”
BackgroundInfluentialA pan-European study of SARS-CoV-2 variants in wastewater under the EU Sewage Sentinel System
Agrawal, S., Orschler, L., Schubert, S., et al. (2021) · medRxiv · doi:10.1101/2021.06.11.21258756 · Cited by 14
Ramphul, K., Ramphul, Y., Park, Y., Lohana, P. J. D., Dhillon, B. K., & Sombans, S. (2021) · Archives of Medical Science - Atherosclerotic Diseases · doi:10.5114/amsad.2021.105065 · Cited by 17
“It has an N501Y mutation in the spike protein [12, 20].”
BackgroundHard choices: Ethical challenges in phase 1 of COVID-19 vaccine roll-out in South Africa.
Moodley, K., Blockman, M., Pienaar, D., et al. (2021) · South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde · doi:10.7196/samj.2021.v111i6.15593 · Cited by 14
Self-citationMolecular strategies for antibody binding and escape of SARS-CoV-2 and its mutations
Hendy, M. A., Kaufman, S., & Ponga, M. R. (2021) · Scientific Reports · doi:10.1038/s41598-021-01081-0 · Cited by 17
ESC - a comprehensive resource for SARS-CoV-2 immune escape variants
Rophina, M., Pandhare, K., Shamnath, A., et al. (2021) · bioRxiv · doi:10.1101/2021.02.18.431922 · Cited by 14
Salvato, R., Gregianini, T., Campos, A., et al. (2021) · Revista de Epidemiologia e Controle de Infecção · doi:10.21203/rs.3.rs-280297/v1 · Cited by 14
“325 (K417N/T, E484K, N501Y) lineages that emerged in the United Kingdom and South Africa and were associated to increased transmissibility [2, 3].”
BackgroundYang, Y., Li, W., Liu, K., Xue, H., Yu, R., Zhang, M., Bao, Y., Lai, X., Fan, J., Huang, Y., et al. (2023) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2023.05.011 · Cited by 16
“351) has since spread to 113 countries with great concern in its immune escape [12,13].”
BackgroundA comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study
Anscombe, C., Lissauer, S., Thole, H., Rylance, J., Dula, D., Menyere, M., Kutambe, B. M., van der Veer, C., Phiri, T., Banda, N. P. K., et al. (2023) · BMC Infectious Diseases · doi:10.1186/s12879-022-07941-y · Cited by 22
“The evolution of the virus has led to the emergence of lineages designated as VOCs, which are defined using genome sequencing and the widespread use of genomic surveillance to inform public health strategy has been a defining feature of the pandemic [8, 9].”
BackgroundCarpi, G., Gorenstein, L., Harkins, T. T., Samadi, M., & Vats, P. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac314 · Cited by 13
Delshad, M., Sanaei, M., Pourbagheri‐Sigaroodi, A., & Bashash, D. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109128 · Cited by 18
“351 variant in South Africa was the interaction of the virus with HIV; although it seems that HIV infection could not affect SARS-CoV-2 replication, further evaluation is still required in this field [197,201].”
Setz, C., Große, M., Auth, J., Fröba, M., Rauch, P., Bausch, A., Wright, M. B., & Schubert, U. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126830 · Cited by 15
Kibria, K. M. K., Faruque, M. O., Islam, M. S. B., Ullah, H., Mahmud, S., Miah, M., & Saleh, A. A. (2022) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-022-11988-x · Cited by 16
van der Velden, Y. U., Grobben, M., Caniels, T. G., Burger, J. A., Poniman, M., Oomen, M., Rijnstra, E. S.-V., Tejjani, K., Guerra, D., Kempers, R., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-07590-w · Cited by 21
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Farley, S., Kyle, J., Leier, H., et al. (2022) · bioRxiv · doi:10.1101/2022.02.14.480430 · Cited by 13
Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice
Walls, A. C., VanBlargan, L. A., Wu, K., Choi, A., Navarro, M. J., Lee, D. W., Avena, L. E., Berrueta, D. M., Pham, M. N., Elbashir, S. M., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111299 · Cited by 13
“As variants of SARS-CoV-2 emerge (Cameroni et al., 2021; Collier et al., 2021; Mlcochova et al., 2021; Tegally et al., 2020; Walls et al., 2022), it is necessary to evaluate their impact on serum neutralizing activity, as a proxy”
Sabin, A. P., Richmond, C. S., & Kenny, P. A. (2022) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2022.115656 · Cited by 12
“Given concerns surrounding multiple other lineages containing this variant [6,29], we analyzed household contacts of this case.”
Oluwagbemi, O. O., Oladipo, E. K., Dairo, E. O., Ayeni, A. E., Irewolede, B. A., Jimah, E. M., Oyewole, M. P., Olawale, B. M., Adegoke, H. M., & Ogunleye, A. J. (2022) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2022.100845 · Cited by 17
Elmorsy, M. A., El-Baz, A. M., Mohamed, N. H., et al. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-16427-4 · Cited by 15
“…strains of SARS-CoV-2 virus in some countries like the UK, South Africa, Brazil, and India which may require further investigation to examine the effectiveness of the developed vaccines against the emerged mutants of COVID-19 (Gómez et al. 2021; Hu et al. 2021; Wise 2020; Tegally et al. 2020).”
BackgroundMasindi, V., Foteinis, S., Nduli, K., & Akinwekomi, V. (2021) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2021.149298 · Cited by 18
The Immunopathobiology of SARS-CoV-2 Infection
Patel, M., Shahjin, F., Cohen, J. D., Hasan, M., Machhi, J., Chugh, H., Singh, S., Das, S., Kulkarni, T. A., Herskovitz, J., et al. (2021) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuab035 · Cited by 15
“Therefore, clinical observations, patient history, and epidemiological information must also be considered to evaluate test results or employ alternative diagnostic tests for re-confirmation (Tegally et al. 2020) (Fig.”
BackgroundFukuzawa, K., Kato, K., Watanabe, C., Kawashima, Y., Handa, Y., Yamamoto, A., Watanabe, K., Ohyama, T., Kamisaka, K., Takaya, D., et al. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00694 · Cited by 27
High‐resolution melting curve FRET‐PCR rapidly identifies SARS‐CoV‐2 mutations
Barua, S., Hoque, M. M., Kelly, P. J., Bai, J., Hanzlicek, G., Noll, L. W., Walz, H., Johnson, C. M., Kyriakis, C. S., & Wang, C. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27139 · Cited by 21
Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman PrimatesPreprint
Corbett, K. S., Werner, A. P., Connell, S. O., Gagné, M., Lai, L., Moliva, J. I., Flynn, B. J., Choi, A., Koch, M. J., Foulds, K. E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.21.445189 · Cited by 11
Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man
Fabiani, M., Margiotti, K., Viola, A., Mesoraca, A., & Giorlandino, C. (2021) · Pathogens · doi:10.3390/pathogens10050614 · Cited by 10
“The SARS-CoV-2 P.1 variant has a unique genetic profile of 17 amino acid changes, including three mutations (E484K, K417T, and N501Y) in the receptor-binding domain (RBD) region that are also present in the B.1.325 variant, a recent lineage that first emerged in South Africa [3].”
BackgroundInfluentialInferring the Main Drivers of SARS‐CoV‐2 Global Transmissibility by Feature Selection Methods
Djordjevic, M., Salom, I., Markovic, S., et al. (2021) · GeoHealth · doi:10.1029/2021gh000432 · Cited by 13
“Despite the unprecedented worldwide campaign of mass immunization, due to the relatively slow vaccine rollout and to the appearance of new, more contagious (Tegally et al., 2020), and maybe even more deadly SARS-CoV-2 strains (Mallapaty, 2021), COVID-19 still takes its toll on human lives, stifles the world economy, a…”
BackgroundCyanobacterial natural products as sources for antiviral drug discovery against COVID-19
Porzani, S. J., Konur, O., & Nowruzi, B. (2021) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2021.1899050 · Cited by 15
“On 28 December 2020, one additional case of this new variant was detected in Finland in a returning traveler from South Africa (Abdool Karim, 2020; Tegally et al., 2020).”
Background
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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