Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species

Wang, Ruoke; Zhang, Qi; Ge, Jiwan; Ren, Wenlin; Zhang, Rui; Lei, Jun; Ju, Bin; Su, Bin; Yu, Fang; Chen, Peng; Liao, Huiyu; Feng, Yingmei; Li, Xuemei; Shi, Xuanling; Zhang, Zheng; Zhang, Fujie; Ding, Qiang; Zhang, Tong; Wang, Xinquan; Zhang, Linqi

doi:10.1016/j.immuni.2021.06.003

Cited by 204 publications

(218 citation statements)

References 74 publications

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“…However, the overrepresentation of functionally important spike mutations including NTD deletions ΔH69-V70 and ΔY144 together with RBD mutations K417X, S477X, E484X, and N501X as well as P681X (near the S1/S2 interface) in the absence of a clear elevation of VOCs or VOIs may indicate a starting sieve effect at individual or combinations of functional mutations. Spike mutations and deletions reported to confer neutralization escape in vitro 23,43,44 might thus be responsible for a sieve effect in a real-life situation, i.e., among vaccinated individuals.…”

Section: Discussionmentioning

confidence: 99%

“…The B.1.1.7 variant, e.g., through the RBD N501Y mutation but also through NTD deletions, acquired an enhanced affinity to ACE2, higher infectivity and virulence [54][55][56][57] , while maintaining sensitivity to neutralization though with slightly impaired nAb titers 54,[58][59][60] . The B.1.526 variant and its derivatives were designated VOI because of the presence of RBD mutations such as E484K or S477N that favor immune evasion 23,25 .…”

Section: Discussionmentioning

confidence: 99%

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Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

Duerr

Dimartino

Marier

et al. 2021

Preprint

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The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 67 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. Their median age was 45 years; seven required hospitalization and one died. Most breakthrough infections (54/67) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 5 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in chi-squared and McNemar tests (p>0.1) highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-Co-V2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

Duerr

Dimartino

Marier

et al. 2021

Preprint

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“…In addition, the reducing in neutralizing was observed in variants with mutations in NTD region and convalescent plasma. Although the results could not necessarily equivalent to natural infection and transmission, these mutations probably cause advantage to the virus (Wang et al, 2021) .…”

Section: Discussionmentioning

confidence: 86%

Predominance of SARS-CoV-2 P.1 (Gamma) lineage inducing the recent wave in southern Brazil and the finding of an additional S: D614A mutation

Demoliner

Silva

Gularte

et al. 2021

Preprint

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Since the first SARS-CoV-2 case in China in late 2019, this virus continues to impact many countries worldwide. Recently, the highest wave of SARS-CoV-2 epidemic was registered in Rio Grande do Sul (RS) State, Southern Brazil, considering the number of cases, deaths and hospitalization per day caused by COVID-19. In this study we described which lineages were circulating in the beginning of 2021 in southern Brazil to understand the cause of the highest health crisis caused by SARS-CoV-2 in the region, searching also possible additional SARS-CoV-2 sequence mutation. A total of 71 positive SARS-CoV-2 samples collected between December 15th, 2020, until April 23rd, 2021, were selected to sequencing. The samples were from 16 cities distributed in three RS regions. The library preparation was performed according to QIAseq® SARS-CoV-2 Primer Panel Handbook kit, and phylogenetic analysis was realized. Whole genome sequencing of 71 SARS-CoV-2 samples shows a predominance of Gamma lineage (67.14%, 47/71), followed by Zeta lineage (27.14%, 20/71) and B.1.1.28 (5,71%, 4/71). Two Gamma lineage consensus sequences presented a D614A mutation. Newly mutations could be emerging due the quick SARS-CoV-2 spreading. Thus, the greater understanding about immune protection and variants vigilance is essential to the better management of the health SARS-CoV-2 crisis.

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“…To date (mid-2021), B.1.351 and P.1 are the most resistant variants to anti-SARS-CoV-2 nAb responses, and notably, they also acquired the ability to use ACE from other species, thus extending the host range to mice and minks [ 397 , 398 ]. As shown for P.1 variants in Brazil, VOCs may also facilitate coinfections with different SARS-CoV-2 lineages [ 399 ].…”

Section: Humoral Immune Responsesmentioning

confidence: 99%

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

2021

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SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale, causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics, delineating their distinct strategies for efficient spread.

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Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species

Cited by 204 publications

References 74 publications

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

Dominance of Alpha and Iota variants in SARS-CoV-2 vaccine breakthrough infections in New York City

Predominance of SARS-CoV-2 P.1 (Gamma) lineage inducing the recent wave in southern Brazil and the finding of an additional S: D614A mutation

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

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