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

Tegally, Houriiyah; Wilkinson, Eduan; Giovanetti, Marta; Iranzadeh, Arash; Fonseca, Vagner; Giandhari, Jennifer; Doolabh, Deelan; Pillay, Sureshnee; San, Emmanuel James; Msomi, Nokukhanya; Mlisana, Koleka; Gottberg, Anne von; Walaza, Sibongile; Allam, Mushal; Ismail, Arshad; Mohale, Thabo; Glass, Allison; Engelbrecht, Susan; Zyl, Gert van; Preiser, Wolfgang; Petruccione, Francesco; Sigal, Alex; Hardie, Diana; Marais, Gert; Hsiao, Marvin; Korsman, Stephen N.J.; Davies, Mary‐Ann; Tyers, Lynn; Mudau, Innocent; York, Denis; Maslo, Caroline; Goedhals, Dominique; Abrahams, Shareef; Laguda-Akingba, Oluwakemi; Alisoltani-Dehkordi, Arghavan; Godzik, Adam; Wibmer, Constantinos Kurt; Sewell, B. Trevor; Lourenço, José; Alcântara, Luiz Carlos Júnior; Pond, Sergei L. Kosakovsky; Weaver, Steven; Martin, Darren P.; Lessells, Richard; Bhiman, Jinal N.; Williamson, Carolyn; Oliveira, Túlio de

doi:10.1101/2020.12.21.20248640

Cited by 979 publications

(1,053 citation statements)

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“…A number of circulating SARS-CoV-2 variants that have been associated with rapidly increasing case numbers and have particular prevalence in the UK (B.1.1.7/501Y.V1), South Africa (B.1.351/501Y.V2) and Brazil (P.1) 14,17,18,36 . Our experiments indicate that the RBD mutations found in these variants, and potentially others that carry K417N/T, E484K and N501Y mutations, can reduce the neutralization potency of vaccinee and convalescent plasma against SARS-CoV-2 pseudotyped viruses.…”

Section: Discussionmentioning

confidence: 99%

“…To determine whether plasma from vaccinated individuals can neutralize circulating SARS-CoV-2 variants of concern and mutants that arise in vitro under antibody pressure 12,13 , we tested vaccinee plasma against a panel of 10 mutant pseudotype viruses including recently reported N501Y (B1.1.7 variant), K417N, E484K and the combination of these 3 RBD mutations (501Y.V2 variant) [14][15][16][17][18][19] . Vaccinee plasma was significantly less effective in neutralizing the HIV-1 virus pseudotyped with certain SARS-CoV-2 mutant S proteins ( Fig.…”

Section: Vaccine Plasma Binding and Neutralizing Activity Against Sarmentioning

confidence: 99%

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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

280

313

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To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Vaccine Plasma Binding and Neutralizing Activity Against Sarmentioning

confidence: 99%

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Wang

Schmidt

Weisblum

et al. 2021

Preprint

280

313

View full text Add to dashboard Cite

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“…Recently, a variant N501Y in the Spike has been reported in the United Kingdom, which is located in the RBD and the impact on the transmission or severity is not known (Kemp et al, 2020;Wise, 2020). From the Costa Rican sequenced cases, none harbors yet this mutation, neither the variant 501Y.V2 described in South Africa (Tegally et al, 2020). Also, a European cluster (called 20A.EU1) has been reported with a significant spread in summer 2020, mainly in Spain (Hodcroft et al, 2020).…”

Section: Other Variantsmentioning

confidence: 99%

SARS-CoV-2 Genomic Surveillance in Costa Rica: Evidence of a Divergent Population and an Increased Detection of a Spike T1117I Mutation

Molina-Mora

Cordero-Laurent

Godínez

et al. 2020

Preprint

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Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. Costa Rica was first exemplary for the region in its pandemic control, declaring a swift state of emergency on March 16th that led to a low quantity of cases, until measures were lifted in early May. From the first detected case in March 6th to December 31st almost 170 000 cases have been reported in Costa Rica, 99.5% of them from May onwards. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave.Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) are predominant, with phylogenetic relationships that are in line with the results of other Latin American countries, suggesting introduction and multiple re-introductions from other regions of the world. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants. These correspond mostly to non-synonymous mutations (51.6%, 146) but 45.6% (129) corresponded to synonymous mutations. The 283 variants showed an expected power-law distribution: 190 single nucleotide mutations were identified in single sequences, only 16 single nucleotide mutations were found in >5% sequences, and only two mutations in >50% genomes. These mutations were distributed through the whole genome. However, 63.6% were present in ORF1ab, 11.7% in Spike gene and 10.6% in the Nucleocapsid gene. Additionally, the prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in all the 2020. Structural modeling of the Spike protein with the T1117I mutation suggest a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. Nevertheless, in-vitro experiments are required to support these in-silico findings. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of COVID-19 pandemic in Costa Rica suggest introduction of lineages from other countries as travel bans and measures were lifted, similar to results found in other studies, as well as an increase in the Spike-T1117I variant that needs to be monitored and studied in further analyses as part of the surveillance program during the pandemic.

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“…These variants harbor one or several non-synonymous spike mutations including amino-acid replacements at key sites in the spike RBD domain (K417N, E484K, N501Y for the African strain [15] and only N501Y in this region of the protein for the UK strain [16]). The proportion of these variants has increased rapidly and recent observations suggests that they are significantly more transmissible than previously circulating variants.…”

Section: Introductionmentioning

confidence: 99%

In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-Spike RBD interface

Villoutreix

Cálvez

Marcelin

et al. 2021

Preprint

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SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor and several in silico methods to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both UK and South African strains) should be favorable for the interaction with ACE2 while the K417N and E484K substitutions (South African) would seem unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the predicted less favorable (regarding binding) K417N and E484K Spike replacements. Our finding suggests that, if indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions outside the direct Spike-ACE2 interface.HihglightsTransmission of the UK and possibly South African SARS-CoV-2 strains appears substantially increased compared to other variantsThis could be due, in part, to increased affinity between the variant Spike proteins and ACE2We investigated in silico the 3D structure of the Spike-ACE2 complex with a focus on Spike K417N, E484K and N501YThe N501Y substitution is predicted to increase the affinity toward ACE2 (UK strain) with subsequent enhanced transmissibility and possibly pathogenicityAdditional substitutions at positions 417 and 484 (South African strain) may pertub the interaction with ACE2 raising questions about transmissibility and pathogenicity

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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

Cited by 979 publications

References 47 publications

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

SARS-CoV-2 Genomic Surveillance in Costa Rica: Evidence of a Divergent Population and an Increased Detection of a Spike T1117I Mutation

In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-Spike RBD interface

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