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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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“A number of spike mutations have been found in newer variations, which raises the possibility of immunological escape (Naveca et al., 2021; Tegally et al., 2020).”
Lina, B. (2021) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/j.banm.2021.11.002 · Cited by 6
Osnes, M. N., Alfsnes, K., Bråte, J., García, I., Riis, R. K., Instefjord, K. H., Elshaug, H., Vollan, H. S., Moen, L. V., Pedersen, B. N., et al. (2021) · Virus Evolution · doi:10.1093/ve/veab086 · Cited by 11
“The second half of 2020 was also characterized by parallel regional sweeps of P.1 in South America (Gamma variant) (Faria et al. 2021) and B.1.351 (Beta variant) in Africa (Tegally et al. 2020; O’Toole et al. 2021), both of which being less efficiently inhibited by neutralizing antibodies (Hoffmann et al. 2021).”
InfluentialMutations that adapt SARS-CoV-2 to mustelid hosts do not increase fitness in the human airwayPreprint
Zhou, J., Peacock, T. P., Brown, J. C., Goldhill, D. H., Elrefaey, A. M. E., Penrice-Randal, R., Cowton, V. M., Lorenzo, G. D., Furnon, W., Harvey, W. T., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.20.456972 · Cited by 5
Januszewski, M., Ziuzia-Januszewska, L., Santor-Zaczyńska, M., Jakimiuk, A. A., Oleksik, T., Pokulniewicz, M., Pluta, K., Wierzba, W., & Jakimiuk, A. J. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10163724 · Cited by 10
“351 which is also known as South African mutation, and P1 (the Brazilian mutation) rapidly increase within local populations and their higher transmissibility has been confirmed [44,45].”
BackgroundOtaki, J., Nakasone, W., & Nakamura, M. (2021) · COVID · doi:10.21203/rs.3.rs-637436/v1 · Cited by 6
“V2; WHO label Beta) (seven additional point mutations) [49].”
BackgroundDesign of specific primer sets for SARS-CoV-2 variants using evolutionary algorithms
Lopez‐Rincon, A., Perez-Romero, C. A., Mendoza‐Maldonado, L., Claassen, E., Garssen, J., Kraneveld, A. D., & Tonda, A. P. (2021) · Genetic and Evolutionary Computation Conference (GECCO) · doi:10.1145/3449639.3459359 · Cited by 3
Whittaker, C., Watson, O. J., Álvarez, C., Angkasekwinai, N., Boonyasiri, A., Triana, L. C., Chanda, D. M., Charoenpong, L., Chayakulkeeree, M., Cooke, G., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab837 · Cited by 8
Erster, O., Mendelson, E., Levy, V., et al. (2021) · medRxiv · doi:10.1101/2021.05.19.21257439 · Cited by 6
“In vitro studies also show that it has increased resistance to serum of recovered and vaccinated patients, thereby posing a serious threat on the efficacy of current vaccination campaigns (6-8).”
BackgroundHughes, S. D., Woods, W. J., O’Keefe, K. J., Delgado, V., Pipkin, S. S., Scheer, S., & Truong, H. M. (2021) · Journal of Mixed Methods Research · doi:10.1177/15586898211012786 · Cited by 6
“This circumstance, however, is often the case with qualitative research, which does not typically claim to be exhaustive and generalizable (Pope & Mays, 1995; Tracy, 2010).”
BackgroundSurging COVID-19 in Bangladesh driven by B.1.351 variantPreprint
Brum, E., Saha, S., Sania, A., Tanmoy, A. M., Hooda, Y., Tanni, A. A., Goswami, S., Sium, S. M. A., Sajib, M. S. I., Malaker, R., et al. (2021) · medRxiv · doi:10.1101/2021.04.27.21255706 · Cited by 6
Çetin, Ş., Ülgen, A., BALCI, P., Şıvgın, H., Çetin, M., ŞIVGIN, S., & Li, W. (2021) · SciMedicine Journal · doi:10.28991/scimedj-2021-03-si-1 · Cited by 6
Substantial impact of post-vaccination contacts on cumulative infections during viral epidemics
Rochman, N. D., Wolf, Y. I., & Koonin, E. V. (2021) · F1000Research · doi:10.12688/f1000research.52341.2 · Cited by 9
Lopez, E., Haycroft, E., Adair, A., et al. (2021) · medRxiv · doi:10.1101/2021.03.20.21254037 · Cited by 6
“As we enter the second year of the SARS68 CoV-2 pandemic, and promising vaccines are rolled out (4, 5), the ongoing 69 transmission along with the emergence of new variants with multiple mutations at key 70 residues in the spike glycoprotein (6-8), has resulted in the continued implementation 71 of stringent public he…”
Schepens, B., van Schie, L., Nerinckx, W., Roose, K., Breedam, W. V., Fijałkowska, D., Devos, S., Weyts, W., Cae, S. D., Vanmarcke, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.08.433449 · Cited by 7
ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7Preprint
Fischer, R. J., van Doremalen, N., Adney, D. R., Yinda, C. K., Port, J. R., Holbrook, M. G., Schulz, J. E., Williamson, B. N., Thomas, T., Barbian, K., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.11.435000 · Cited by 29
Kharchenko, E. P. (2021) · Epidemiology and Vaccinal Prevention · doi:10.31631/2073-3046-2021-20-1-4-19 · Cited by 8
Giorgi, E. E., Tanmoy Bhattacharya, A., Fischer, W., Yoon, H., Abfalterer, W., & Korber, B. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.29.428535 · Cited by 5
D614G substitution at the hinge region enhances the stability of trimeric SARS-CoV-2 spike protein
Yazhini, A., Sidhanta, D. S. P., & Srinivasan, N. (2021) · Bioinformation · doi:10.6026/97320630017439 · Cited by 7
Matson, R. P., Comba, I. Y., Silvert, E., Niesen, M. J. M., Murugadoss, K., Patwardhan, D., Suratekar, R., Goel, E.-G., Poelaert, B. J., Wan, K. K., et al. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00471-0 · Cited by 5
“Furthermore, in an era where there is a signi fi cant amount of viral surveillance data 18 – 20 , modeling approaches can be used to extract valuable knowledge about viral properties and antibody escape that may not be entirely captured by conventional methods.”
Liang, Y., Sun, Q., Liu, Q., Pang, Y., & Tang, S. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1044788 · Cited by 7
Focused Review: Insight and Updates on COVID-19 from Progress in Microbes and Molecular Biology
Thye, A. Y.-K., & Law, J. W. (2023) · Progress In Microbes & Molecular Biology · doi:10.36877/pmmb.a0000333 · Cited by 6
“B.1.351 has higher transmissibility, viral load, reinfection, vaccine escape, hospitalisation rate, and mortality than the progenitor strain [10,94,99–102] .”
InfluentialShipulin, G. A., Savochkina, Y. A., Shuryaeva, A. K., Glushchenko, E. E., Luparev, A. R., Polyakova, V. A., Danilov, D., Евгеньевна, Д. Е., Vinogradov, K. S., Stetsenko, I. F., et al. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e16917 · Cited by 6
Adeniyi, O. V., Durojaiye, O. C., & Masilela, C. M. (2023) · Vaccines · doi:10.3390/vaccines11061068 · Cited by 5
Physical-Chemical Regulation of Membrane Receptors Dynamics in Viral Invasion and Immune Defense
Qin, R., An, C., & Chen, W. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167800 · Cited by 6
Mutational induction in SARS-CoV-2 major lineages by experimental exposure to neutralising sera
Brandolini, M., Dirani, G., Taddei, F., Zannoli, S., Denicolò, A., Arfilli, V., Battisti, A., Manera, M., Mancini, A., Grumiro, L., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-16533-4 · Cited by 5
Novel Lateral Flow-Based Assay for Simple and Visual Detection of SARS-CoV-2 Mutations
Gomez-Martinez, J., Henry, S., Tuaillon, É., de Perre, P. V., Fournier‐Wirth, C., Foulongne, V., & Brès, J.-C. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.902914 · Cited by 6
Chiang, C.-Y., Chen, M., Hsu, C.-W., Liu, C., Tsai, Y.-W., Liao, H., Yan, J., Chuang, Z.-S., Wang, H.-I., Pan, C.-H., et al. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00823-0 · Cited by 6
Boukadida, C., Taboada, B., Escalera‐Zamudio, M., Iša, P., Ramírez–González, J. E., Vázquez-Pérez, J. A., Muñoz‐Medina, J. E., Grajales-Muñíz, C., González-Torres, C., Gaytán-Cervantes, J., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.01249-21 · Cited by 4
Herlinger, A. L., Monteiro, F. L. L., D’arc, M., Moreira, F. R. R., Westgarth, H. J., Galliez, R. M., Mariani, D., da Costa, L. J., de Almeida, L. G. P., Voloch, C. M., et al. (2021) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/0074-02760210176 · Cited by 7
Structural Insights of SARS-CoV-2 Spike Protein from Delta and Omicron VariantsPreprint
Sadek, A. H., Zaha, D., & Ahmed, M. S. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.12.08.471777 · Cited by 8
“Although the viral evolution is slowed by the RNA proofreading capability of its replication machinery [12], several variants of interest (VOI) or concern (VOC) were discovered at the S protein surface including Alpha, Beta, Gamma, Delta, Lambda, Mu, and most recently Omicron [13-17].”
BackgroundEmergence of a novel SARS-CoV-2 Pango lineage B.1.1.526 in West Bengal, India
Sarkar, R., Saha, R., Mallick, P., Sharma, R. P., Kaur, A., Dutta, S., & Chawla‐Sarkar, M. (2021) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2021.11.020 · Cited by 6
A case series of SARS-CoV-2 reinfections caused by the variant of concern Gamma in BrazilPreprint
Naveca, F. G., do Nascimento, V. A., Nascimento, F., Ogrzewalska, M., Pauvolid‐Corrêa, A., de Araújo, M. F., Arantes, I., Batista, É. L. R., Magalhães, A. L. Á., Vinhal, F. A., et al. (2021) · medRxiv · doi:10.1101/2021.11.29.21266109 · Cited by 5
Genetic Path of the Emergence of SARS-CoV-2
Nasrin, T., & Ali, S. (2021) · Gene Cell and Tissue · doi:10.5812/gct.118302 · Cited by 8
Mak, G. C. K., Lau, S., Wong, K. K. Y., et al. (2021) · Journal of Clinical Virology · doi:10.1016/j.jcv.2021.104994 · Cited by 5
The Delta Variant Had Negligible Impact on COVID-19 Vaccine Effectiveness in the USAPreprint
Blaiszik, B., Graziani, C., Olds, J., & Foster, I. T. (2021) · medRxiv · doi:10.1101/2021.09.18.21263783 · Cited by 5
“V2), first identified in the Republic of South Africa in December 2020 [19]; the P.”
BackgroundYu, J., Azzam, E. I., Jadhav, A. B., & Wang, Y. (2021) · Cells · doi:10.3390/cells10092212 · Cited by 6
“However, variants with Y453F (tyrosine substituted by phenylalanine at position 453) mutation on the S protein are still common in the Netherlands and have been reported sporadically in several other countries including the Russian Federation, South Africa, Switzerland, and the USA [111].”
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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