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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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Ryu, D.-K., Song, R., Kim, M., Kim, Y., Kim, C.-M., Kim, J., Kwon, K.-S., Tijsma, A. S. L., Nuijten, P. M., van Baalen, C. A., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.06.016 · Cited by 55
The evolutionary dynamics of endemic human coronaviruses
Jo, W. K., Drosten, C., & Drexler, J. F. (2021) · Virus Evolution · doi:10.1093/ve/veab020 · Cited by 60
Tablizo, F. A., Kim, K. M., Lapid, C. M., Castro, M. J. R., Yangzon, M. S. L., Maralit, B. A., Ayes, M. E. C., Cutiongco-de la Paz, E. M., De Guzman, A. R., Yap, J. M. C., et al. (2021) · doi:10.1101/2021.03.03.21252812 · Cited by 46
Partial resistance of SARS-CoV-2 Delta variants to vaccine-elicited antibodies and convalescent sera
Tada, T., Zhou, H., Dcosta, B. M., Samanovic, M. I., Mulligan, M. J., & Landau, N. R. (2021) · iScience · doi:10.1016/j.isci.2021.103341 · Cited by 101
“The L452R mutation is present in the California B.1.427/B.1.429 variant and was found to cause a 2-fold increase in virus shedding by infected individuals, increased infectivity in cell culture, and a 4- to 6.7-fold and 2-fold decrease in neutralizing titer by the antibodies of convalescent and vaccinated donors, resp…”
BackgroundInfluentialÇeli̇k, İ., Yadav, R., Düzgün, Z., Albogami, S. M., El‐Shehawi, A. M., Fatimawali, F., Idroes, R., Tallei, T. E., & Emran, T. B. (2021) · Biology · doi:10.3390/biology10090880 · Cited by 49
Lubinski, B., Fernandes, M. H. V., Frazier, L. E., Tang, T., Daniel, S., Diel, D. G., Jaimes, J. A., & Whittaker, G. R. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3889709 · Cited by 31
Staquicini, D. I., Tang, F. H. F., Markosian, C., Yao, V. J., Staquicini, F. I., Dodero‐Rojas, E., Contessoto, V. G., Davis, D., O’Brien, P., Habib, N., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2105739118 · Cited by 69
“Of note, epitope 4 is unchanged in three main emergent SARS-CoV-2 viral lineages: Alpha, first identified in the United Kingdom (52), Beta, first identified in South Africa (53), and Gamma, first identified in Brazil (54).”
The role of airborne particles and environmental considerations in the transmission of SARS-CoV-2
Shao, L., Ge, S., Jones, T. P., Santosh, M., Silva, L. F. O., Cao, Y., Oliveira, M. L. S., Zhang, M., & BéruBé, K. (2021) · Geoscience Frontiers · doi:10.1016/j.gsf.2021.101189 · Cited by 53
“In Brazil and South Africa, new mutations of viruses have also been reported (Koyama et al., 2020; Tegally et al., 2020; Sabino et al., 2021; Tang et al., 2021).”
BackgroundThe impact of Spike mutations on SARS-CoV-2 neutralizationPreprint
Rees-Spear, C., Muir, L., Griffith, S. A., Heaney, J., Aldon, Y., Snitselaar, J. L., Pataillot-Meakin, T., Graham, C., Seow, J., Lee, N., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.15.426849 · Cited by 45
Fratev, F. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.23.424283 · Cited by 68
“In addition, an enhancement of the virus transmission in humans of about 70% and even worse were reported [1-2, 4-5].”
BackgroundSkelly, D. T., Harding, A. C., Gilbert-Jaramillo, J., Knight, M. L., Longet, S., Brown, A., Adele, S., Adland, E., Brown, H., Team, M. L., et al. (2021) · doi:10.21203/rs.3.rs-226857/v1 · Cited by 216
Abebe, E. C., & Dejenie, T. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1055457 · Cited by 58
Fédry, J., Hurdiss, D. L., Wang, C., Li, W., Obal, G., Drulyte, I., Du, W., Howes, S. C., van Kuppeveld, F. J. M., Förster, F. G., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf5632 · Cited by 54
Summary of the Available Molecular Methods for Detection of SARS-CoV-2 during the Ongoing Pandemic
Arena, F., Pollini, S., Rossolini, G. M., & Margaglione, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031298 · Cited by 48
Mullick, B., Magar, R., Jhunjhunwala, A., & Farimani, A. B. (2021) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2021.104915 · Cited by 49
“Moreover, higher local flexibility regions have an increased value of entropy and are prone to mutations [21].”
Zhuang, X., Tsukuda, S., Wrensch, F., Wing, P. A. C., Schilling, M., Harris, J. M., Borrmann, H., Morgan, S. B., Cane, J., Mailly, L., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103144 · Cited by 63
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Rothenberger, S., Hurdiss, D. L., Walser, M., Malvezzi, F., Mayor, J., Ryter, S., Moreno, H., Liechti, N., Bosshart, A., Iss, C., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01382-3 · Cited by 75
Rahman, F. I., Ether, S. A., & Islam, M. R. (2021) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2021-0251 · Cited by 51
“351 (WHO label: Beta) has three concerning mutations (N501Y, E484K, and K417N) in its spike protein and it spread like wildfire in South Africa [6] due to its increased transmission rate and potential to escape antibodies [7].”
BackgroundInfluentialStoddard, C. I., Galloway, J., Chu, H. Y., Shipley, M. M., Sung, K., Itell, H. L., Wolf, C. R., Logue, J. K., Magedson, A., Garrett, M. E., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109164 · Cited by 52
Amanat, F., Thapa, M., Lei, T., Ahmed, S. M. S., Adelsberg, D. C., Carreño, J. M., Strohmeier, S., Schmitz, A. J., Zafar, S., Zhou, J. Q., et al. (2021) · medRxiv · doi:10.1101/2021.03.07.21253098 · Cited by 41
SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection
Bashor, L., Gagne, R., Bosco-Lauth, A., et al. (2021) · bioRxiv · doi:10.1101/2021.03.05.434135 · Cited by 48
Edara, V. V., Norwood, C., Floyd, K. A., Lai, L., Davis-Gardner, M. E., Hudson, W. H., Mantus, G. E., Nyhoff, L. E., Adelman, M. W., Fineman, R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.20.432046 · Cited by 37
“In particular, the emergence of the B.1.351 variant, which was originally identified in South Africa, includes several mutations within the structural and nonstructural proteins (Tegally et al., 2020).”
BackgroundInfluentialEstimates of anti-SARS-CoV-2 antibody seroprevalence in Iran
Ghafari, M., Kadivar, A., & Katzourakis, A. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00053-0 · Cited by 11
Muecksch, F., Weisblum, Y., Barnes, C. O., Schmidt, F., Schaefer-Babajew, D., Lorenzi, J. C. C., Flyak, A. I., DeLaitsch, A. T., Huey-Tubman, K. E., Hou, S., et al. (2021) · doi:10.1101/2021.03.07.434227 · Cited by 39
“associated with SARS-CoV-2 variants with resistance to commonly elicited antibodies (Fujino et al., 2021; Tegally et al., 2020; Volz et al., 2021; Wang et al., 2021; West et al., 2021; Wibmer et al., 2021).”
BackgroundLee, Y. S., Wing, P. A. C., Gala, D., Noerenberg, M., Järvelin, A. I., Titlow, J., Zhuang, X., Palmalux, N., Iselin, L., Thompson, M. K., et al. (2021) · eLife · doi:10.7554/elife.74153 · Cited by 59
The changing face of medical professionalism and the impact of COVID-19
Goddard, A. F., & Patel, M. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00436-0 · Cited by 65
Nambulli, S., Xiang, Y., Tilston-Lunel, N. L., Rennick, L., Sang, Z., Klimstra, W., Reed, D., Crossland, N., Shi, Y., & Duprex, W. P. (2021) · bioRxiv · doi:10.1101/2021.02.23.432569 · Cited by 50
“Finally, as prevalent circulating variants of SARS-CoV-2 have emerged to evade clinical antibodies and wane vaccine-elicited serologic responses (43-47), this proof-of-concept study will shed light on the use of stable, multi-epitope and multivalent Nb constructs, in combination with PiN-21, as a novel aerosol cocktai…”
BackgroundAssessment of SARS-CoV-2 Genome Sequencing: Quality Criteria and Low-Frequency Variants
Jacot, D., Pillonel, T., Greub, G., & Bertelli, C. (2021) · Journal of Clinical Microbiology · doi:10.1128/jcm.00944-21 · Cited by 43
Chung, H., Jian, M., Chang, C.-K., Lin, J., Yeh, K., Chen, C., Hsieh, S., Hung, K., Tang, S. W., Perng, C., et al. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02513-21 · Cited by 84
A molecular sensor determines the ubiquitin substrate specificity of SARS-CoV-2 papain-like protease
Patchett, S., Lv, Z., Rut, W., Békés, M., Drąg, M., Olsen, S. K., & Huang, T. T. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109754 · Cited by 51
Yadav, P. D., Sapkal, G. N., Ella, R., Sahay, R. R., Nyayanit, D. A., Patil, D. Y., Deshpande, G. R., Shete, A. M., Gupta, N., Mohan, V., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.05.447177 · Cited by 39
NeutrobodyPlex—monitoring SARS-CoV-2 neutralizing immune responses using nanobodies
Wagner, T. R., Kaiser, P. D., Gramlich, M., Ostertag, E., Ruétalo, N., Junker, D., Häring, J., Traenkle, B., Becker, M., Dulovic, A., et al. (2021) · EMBO Reports · doi:10.15252/embr.202052325 · Cited by 50
Bugembe, D., V.T.Phan, M., Ssewanyana, I., et al. (2021) · medRxiv · doi:10.1101/2021.02.08.21251393 · Cited by 45
Ongoing Recombination in SARS-CoV-2 Revealed through Genealogical Reconstruction
Ignatieva, A., Hein, J., & Jenkins, P. A. (2022) · Molecular Biology and Evolution · doi:10.1093/molbev/msac028 · Cited by 51
Fröba, M., Große, M., Setz, C., Rauch, P., Auth, J., Spanaus, L., Münch, J., Ruétalo, N., Schindler, M., Morokutti-Kurz, M., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413202 · Cited by 47
SARS‐CoV‐2 virulence evolution: Avirulence theory, immunity and trade‐offs
Alizon, S., & Sofonea, M. T. (2021) · Journal of Evolutionary Biology · doi:10.1111/jeb.13896 · Cited by 53
“Sequencing quickly revealed that it too bore a higher number of mutations than expected based on the mean molecular clock value (Tegally et al., 2020).”
BackgroundGong, W., Aspatwar, A., Wang, S., Parkkila, S., & Wu, X. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1938550 · Cited by 46
Wollschläger, P., Tödt, D., Gerlitz, N., Pfaender, S., Bollinger, T., Sing, A., Dangel, A., Ackermann, N., Korn, K., Ensser, A., et al. (2021) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.05.025 · Cited by 47
“References [1] Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Fonseca V, Giandhari J, et al. 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.”
InfluentialVerkhivker, G. M., Agajanian, S., Öztaş, D. Y., & Gupta, G. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00139 · Cited by 62
Long, S. W., Olsen, R. J., Christensen, P. A., Subedi, S., Olson, R., Davis, J. J., Saavedra, M. O., Yerramilli, P., Pruitt, L., Reppond, K., et al. (2021) · American Journal Of Pathology · doi:10.1016/j.ajpath.2021.03.004 · Cited by 46
“This variant was concerning because of its large number of spike protein mutations (including K417N, E484K, and N501Y) (Figure 1) and apparent increased transmissibility.(16,31) These three mutations are located in the receptor binding domain of spike and may decrease the effectiveness of some monoclonal antibody ther…”
Jassat, W., Mudara, C., Ozougwu, L., Tempia, S., Blumberg, L. H., Davies, M., Pillay, Y. G., Carter, T., Morewane, R., Wolmarans, M., et al. (2021) · medRxiv · doi:10.1101/2021.03.09.21253184 · Cited by 61
Self-citationNeutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera
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Self-citationBiological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences
Hoteit, R., & Yassine, H. M. (2022) · Vaccines · doi:10.3390/vaccines10060919 · Cited by 47
“This variant is 50% (95% CI: 20–113%) more transmissible than the Alpha variant in South Africa, according to a mathematical model [158].”
BackgroundBrunotte, L., Zheng, S., Mecate‐Zambrano, A., Tang, J. P., Ludwig, S., Rescher, U., & Schloer, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13091400 · Cited by 45
Hirotsu, Y., & Omata, M. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009619 · Cited by 40
“351 lineage has become the dominant strain of SARS-CoV-2 in South Africa, where it was first detected in October 2020 [4].”
BackgroundImmunity to SARS-CoV-2: Lessons Learned
FERGIE, J. E., & Srivastava, A. K. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.654165 · Cited by 46
“1 (first observed in Brazil), have arisen and are spreading across the globe (55, 60).”
BackgroundKo, S. H., Mokhtari, E. B., Mudvari, P., Stein, S. R., Stringham, C. D., Wagner, D. A., Ramelli, S. C., Ramos-Benítez, M. J., Strich, J. R., Davey, R. T., et al. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009431 · Cited by 41
Genomic surveillance at scale is required to detect newly emerging strains at an early timepointPreprint
Vavrek, D. A., Speroni, L., Curnow, K. J., Oberholzer, M., Moeder, V., & Febbo, P. G. (2021) · medRxiv · doi:10.1101/2021.01.12.21249613 · Cited by 38
“Tegally H, Wilkinson E, Giovanetti M, et al. 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. medRxiv.”
BackgroundInfluentialFrom Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines
Lopez-Cantu, D. O., Wang, X., Carrasco-Magallanes, H., Afewerki, S., Zhang, X., Bonventre, J. V., & Ruiz‐Esparza, G. U. (2022) · Nano-Micro Letters · doi:10.1007/s40820-021-00771-8 · Cited by 49
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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