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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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“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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
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]
Experimental — accuracy not yet measuredIn the citing paper
“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
“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
“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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Cho, H., Gonzales-Wartz, K. K., Huang, D.-L., Yuan, M., Peterson, M., Liang, J. Y., Beutler, N., Torres, J., Cong, Y., Postnikova, E., et al. (2021) · bioRxiv · doi:10.1101/2021.04.01.437942 · Cited by 10
Early super-spreader events are a likely determinant of novel SARS-CoV-2 variant predominance
Goyal, A., Reeves, D., & Schiffer, J. (2021) · medRxiv · doi:10.1101/2021.03.23.21254185 · Cited by 10
Molecular epidemiology of SARS-CoV-2 in Cyprus
Richter, J., Fanis, P., Tryfonos, C., Koptides, D., Krashias, G., Bashiardes, S., Hadjisavvas, A., Loizidou, M. A., Oulas, A., Alexandrou, D., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248792 · Cited by 11
Surveillance of SARS-CoV-2 in Zimbabwe shows dominance of variants of concern
Mashe, T., Takawira, F. T., Gumbo, H., et al. (2021) · The Lancet Microbe · doi:10.1016/s2666-5247(21)00061-6 · Cited by 10
Adnan, N., Khondoker, M. U., Rahman, M. S., Ahmed, F., Sharmin, S., Sharif, N., Azmuda, N., Akter, S., Nahar, S., Mou, T. J., et al. (2021) · Microbiology Resource Announcements · doi:10.1128/mra.00124-21 · Cited by 9
“The former mutation was reported in the South African variant as an escape mutation (8, 9).”
BackgroundAlter, G., Gorman, M. J., Patel, N., Guebre‐Xabier, M., Zhu, A. L., Atyeo, C. G., Pullen, K. M., Loos, C., Goez-Gazi, Y., Carrion, R., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-200342/v1 · Cited by 9
Lemmermann, N. A. W., Lieb, B., Laufs, T., Renzaho, A., Runkel, S., Kohnen, W., Linke, M., Gerber, S., Schweiger, S., Michel, A., et al. (2021) · medRxiv · doi:10.1101/2021.02.11.21251324 · Cited by 9
“We found N501Y in a genomic background distinct from the known VOCs, thus occurring out of the context of their additional S mutations.”
BackgroundInfluentialVariantes emergentes do SARS-CoV-2 e suas implicações na saúde coletiva
Freitas, A. R. R., Giovanetti, M., & Alcantara, L. C. J. (2021) · InterAmerican Journal of Medicine and Health · doi:10.31005/iajmh.v4i.181 · Cited by 24
“[5] Tegally H, Wilkinson E, Giovanetti M, et al.”
BackgroundInfluentialSelf-citationMiotto, M., Rienzo, L. D., Grassmann, G., Desantis, F., Cidonio, G., Gosti, G., Leonetti, M., Ruocco, G., & Milanetti, E. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1205919 · Cited by 7
“In December 2020 the beta variant (lineage B.1.351) was detected in South Africa (Tegally et al., 2020), even though phylogeographic analysis suggests this variant emerged much sooner, in July or August 2020 (Tegally et al., 2020).”
BackgroundInfluentialRodriguez, J. A., Gonzalez, J., Arboleda-Bustos, C. E., Mendoza, N., Martinez, C., & Pinzón, A. M. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110244 · Cited by 10
Emergence and evolution of SARS-CoV-2 genetic variants during the Cuban epidemic
Tirado, M. G. G., Pérez, L., Tejero, Y., Mederos, D., Aguado, M. E., Pintos, Y., Valdés, O., Álvarez, M., de León, L. D. R. P., Rodríguez, W. B., et al. (2022) · Journal of Clinical Virology Plus · doi:10.1016/j.jcvp.2022.100104 · Cited by 10
Distinct immune responses in the early phase to natural SARS‐CoV‐2 infection or vaccination
Peng, P., Deng, H., Li, Z., Chen, Y., Fang, L., Hu, J., Wu, K., Xue, J., Wang, D., Liu, B., et al. (2022) · Journal of Medical Virology · doi:10.1002/jmv.28034 · Cited by 10
AlMalki, F. A., Albukhaty, S., Alyamani, A. A., Khalaf, M. N., & Thomas, S. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-18868-x · Cited by 13
“The mutated residues stimulate cleavage located in the S1/S2 site, which is considered to provide the dynamic conformational changes that increase the interactions between the S protein and hACE2 receptor (Tegally et al. 2020).”
BackgroundAbdulnoor, M., Eshaghi, A., Perusini, S. J., Broukhanski, G., Corbeil, A., Cronin, K. I., Fittipaldi, N., Forbes, J. D., Guthrie, J. L., Kus, J. V., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.00681-21 · Cited by 9
“A second SARS-CoV-2 VOC representing the B.1.351 lineage (also known as 20H/ 501Y.V2, VOC-202012/02, and Beta) emerged in October 2020 in South Africa (3).”
BackgroundInfluentialWang, S., Zou, X., Li, Z., Fu, J., Fan, H., Yu, H., Dèng, F., Huang, H., Peng, J., Zhao, K., et al. (2021) · Frontiers in Public Health · doi:10.3389/fpubh.2021.791600 · Cited by 8
“The emergence of the Beta variant includes several mutations within the structural and nonstructural proteins (31).”
BackgroundRelative Consolidation of the Kappa Variant Pre-Dates the Massive Second Wave of COVID-19 in India
Singh, J., Malhotra, A. G., Biswas, D., Shankar, P., Lokhande, L., Yadav, A. K., Raghuvanshi, A., Kale, D., Nema, S., Saigal, S., et al. (2021) · Genes · doi:10.3390/genes12111803 · Cited by 10
“This domain, considered important for viral assembly, could favor viral replication in the concerned variants [22,23].”
BackgroundHost Response to SARS-CoV2 and Emerging Variants in Pre-Existing Liver and Gastrointestinal Diseases
Nayak, B., Lal, G., Kumar, S., Das, C. J., Saraya, A., & Shalimar, S. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.753249 · Cited by 9
Near-Complete Genome Sequences of Nine SARS-CoV-2 Strains Harboring the D614G Mutation in Malaysia
Zainulabid, U. A., Kamarudin, N., Zulkifly, A., et al. (2021) · Microbiology Resource Announcements · doi:10.1128/mra.00657-21 · Cited by 9
“351 variant, which harbors the E484K and N501Y mutations commonly associated with increased transmission rate (8).”
BackgroundPrioritizing the vulnerable over the susceptible for COVID‐19 vaccination
Paloyo, S. R., Caballes, A. B., Hilvano-Cabungcal, A. M., et al. (2021) · Developing World Bioethics · doi:10.1111/dewb.12327 · Cited by 9
Wang, J., Yang, Y., Liang, T., Yang, N., Li, T., Zheng, C. J., Ning, N., Luo, D., Yang, X., He, Z., et al. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.07.008 · Cited by 10
“351) in South Africa led to a significant increase in COVID-19 cases [6,7].”
Chiem, K., Vasquez, D. M., Silvas, J. A., Park, J., Piepenbrink, M. S., Sourimant, J., Lin, M. J., Greninger, A. L., Plemper, R. K., Torrelles, J. B., et al. (2021) · Journal of Virology · doi:10.1128/jvi.01126-21 · Cited by 18
The evolving proteome of SARS-CoV-2 predominantly uses mutation combination strategy for survival
Patro, L. P. P., Sathyaseelan, C., Uttamrao, P. P., & Rathinavelan, T. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.05.054 · Cited by 9
Kim, Y.-J., Kim, E., Lee, S., & Kwon, D. (2021) · Osong Public Health and Research Perspectives · doi:10.24171/j.phrp.2021.0037 · Cited by 10
“7 was reported, a similar variant (including N501Y, but not Δ69−70) was reported from South Africa in samples from October 2020 [20] (named the B.”
BackgroundREGEN-COV protects against viral escape in preclinical and human studiesPreprint
Copin, R., Baum, A., Wloga, E. H., Pascal, K. E., Giordano, S., Fulton, B. O., Zhou, A., Negron, N., Lanza, K., Chan, N., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.10.434834 · Cited by 10
Singh, L., Anyaneji, U. J., Ndifon, W. O., Turok, N., Mattison, S. A., Lessells, R. J., Sinayskiy, I., San, E. J., Tegally, H., Barnett, S., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-96934-z · Cited by 9
Self-citationA Novel Immunofluorescence Assay for the Rapid Serological Detection of SARS-CoV-2 Infection
Nguyen, D. V., Skelly, D., & Goonawardane, N. (2021) · Viruses · doi:10.3390/v13050747 · Cited by 11
van der Toorn, W., Oh, D., & von Kleist, M. (2021) · Patterns · doi:10.1016/j.patter.2021.100264 · Cited by 13
The SARS-CoV-2 variant with lineage B.1.351 clusters investigation team (2021) · Eurosurveillance · doi:10.2807/1560-7917.es.2021.26.13.2100333 · Cited by 14
ChAdOx1 nCoV-19 (AZD1222) Vaccine in People Living With and Without HIVPreprint
Madhi, S. A., Koen, A. L., Fairlie, L., Cutland, C., Baillie, V. L., Padayachee, S. D., Dheda, K. U. J., Barnabas, S. L., Bhorat, Q. E., Briner, C., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-322470/v1 · Cited by 10
Evolving Infection Paradox of SARS-CoV-2: Fitness Costs Virulence?
Alam, A., Islam, O. K., Hasan, M. S., et al. (2020) · medRxiv · doi:10.1101/2021.02.21.21252137 · Cited by 9
What chikungunya teaches us about COVID-19
Ramanathan, M., Ferguson, I. D., Miao, W.-L., et al. (2021) · Lancet. Infectious Diseases (Print) · doi:10.1016/s1473-3099(21)00272-3 · Cited by 8
Ramano, E. M., Pretorius, W. P., Jager, M. D., Oldfield, T. O., Scriba, D. S., & Moriti, B. M. (2022) · South African Journal of Occupational Therapy · doi:10.17159/2310-3833/2022/vol52n3a4 · Cited by 7
Carter, C., Airas, J., & Parish, C. A. (2022) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2022.108360 · Cited by 10
“For instance, the Schubert et al. ELISA study used the originally available Q493K mutation and they report slightly decreased binding of the Omicron RBD.”
BackgroundMehra, R., & Kepp, K. P. (2022) · European Biophysics Journal · doi:10.1007/s00249-022-01619-8 · Cited by 10
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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