The basis of a more contagious 501Y.V1 variant of SARS-CoV-2

Liu, Haolin; Zhang, Qianqian; Wei, Pengcheng; Chen, Zhongzhou; Aviszus, Katja; Yang, John Jeongseok; Downing, Walter; Jiang, Chengyu; Liang, Bo; Reynoso, Lyndon; Downey, Gregory P.; Frankel, Stephen K.; Kappler, John W.; Marrack, Philippa; Zhang, Gongyi

doi:10.1038/s41422-021-00496-8

Cited by 143 publications

(139 citation statements)

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“…N501 resides within a field of hAce2 contacts at the rim of the concave binding site (Figure 5c), where it forms one hydrogen bond to tyrosine 41 in hAce2 (Figure 4). A ten-fold affinity gain is brought about by the N501Y mutation as Y501 interacts through a strong, aromatic stacking interaction with Y41 and forms two new hydrogen bonds with D38 and K353 in hAce2 [36]. Moreover, Y501 destabilises the RBD-down conformation, thereby adding to the D614G effect of more open RBDs [37].…”

Section: The D614g Mutation In Spike Facilitates Sars-cov-2 Evolutionmentioning

confidence: 99%

The Spike of Concern—The Novel Variants of SARS-CoV-2

Winger

Caspari

2021

Viruses

107

116

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The high sequence identity of the first SARS-CoV-2 samples collected in December 2019 at Wuhan did not foretell the emergence of novel variants in the United Kingdom, North and South America, India, or South Africa that drive the current waves of the pandemic. The viral spike receptor possesses two surface areas of high mutagenic plasticity: the supersite in its N-terminal domain (NTD) that is recognised by all anti-NTD antibodies and its receptor binding domain (RBD) where 17 residues make contact with the human Ace2 protein (angiotensin I converting enzyme 2) and many neutralising antibodies bind. While NTD mutations appear at first glance very diverse, they converge on the structure of the supersite. The mutations within the RBD, on the other hand, hone in on only a small number of key sites (K417, L452, E484, N501) that are allosteric control points enabling spike to escape neutralising antibodies while maintaining or even gaining Ace2-binding activity. The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open spike protomers in the homo-trimeric receptor complex. This review discusses the recent spike mutations as well as their evolution.

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Section: The D614g Mutation In Spike Facilitates Sars-cov-2 Evolutionmentioning

confidence: 99%

The Spike of Concern—The Novel Variants of SARS-CoV-2

Winger

Caspari

2021

Viruses

107

116

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“…Of the 63 publications included, five were non-peer reviewed preprints [16,17,52,54,66]. Eleven articles reported in vitro, in silico or animal model studies [15,18,19,[22][23][24][25][26][27][28][29]; nineteen articles reported clinical studies [16,[37][38][39][41][42][43][44][45][46][47][48][49]51,[70][71][72][73]. The remaining 33 articles analyzed SARS-CoV-2 genomes downloaded from the GISAID or other available databases with patient status [8][9][10][11]20,21,[30][31][32][33][34][35][36]40,50,…”

Section: Study Selection and Types Of Studiesmentioning

confidence: 99%

“…Twenty-five studies reported the relation between viral mutations and virus load or infectivity of SARS-CoV-2 (Table 2), of which five articles (two in vitro/animal model studies [18,19], two studies based on SARS-CoV-2 genomes downloaded from electronic databases or community-based testing datasets (bigdata analysis) [20,21] and one clinical study [16]) showed no impact of mutations with infectivity of SARS-CoV-2. The remaining 20 studies (nine in vitro/animal model or in silico studies [15,[22][23][24][25][26][27][28][29], eight bigdata analyses [9,[30][31][32][33][34][35][36] and three clinical studies [37][38][39]) showed that SARS-CoV-2 variants were significantly associated with increase in infectivity. All studies performed on the variants of concern (VOCs) have linked these mutations to increased viral transmissibility [23,[27][28][29][34][35][36]38,39], except for one study by Li et al [19].…”

Section: Relation Between Viral Mutation and Infectivity Of Sars-cov-2mentioning

confidence: 99%

“…The remaining 20 studies (nine in vitro/animal model or in silico studies [15,[22][23][24][25][26][27][28][29], eight bigdata analyses [9,[30][31][32][33][34][35][36] and three clinical studies [37][38][39]) showed that SARS-CoV-2 variants were significantly associated with increase in infectivity. All studies performed on the variants of concern (VOCs) have linked these mutations to increased viral transmissibility [23,[27][28][29][34][35][36]38,39], except for one study by Li et al [19]. In this in vitro study, the authors showed a non-significant increase in infectivity in cell lines for any of pseudotyped viruses with the B.1.351 variant compared to the D614G variant [19].…”

Section: Relation Between Viral Mutation and Infectivity Of Sars-cov-2mentioning

confidence: 99%

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SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

Dao

Hoang

Colson

et al. 2021

JCM

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Background: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. Method: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. Results: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. Conclusion: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

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“…Several of the point mutations have been found to lead to increased viral fitness. The N501Y mutation in B.1.1.7 results in increased affinity for ACE2 [7-10] while the E484K mutation in the B.1.351, B.1.526, P.1 and P.3 spike proteins provides partial resistance to neutralizing antibodies in recovered individuals and antibodies elicited by vaccination [11-16].…”

Section: Introductionmentioning

confidence: 99%

The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies

Tada

Zhou

Dcosta

et al. 2021

Preprint

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Highly transmissible SARS-CoV-2 variants recently identified in India designated B.1.617 and B.1.618 have mutations within the spike protein that may contribute to their increased transmissibility and that could potentially result in re-infection or resistance to vaccine-elicited antibody. B.1.617 encodes a spike protein with mutations L452R, E484Q, D614G and P681R while the B.1.618 spike has mutations Δ145-146, E484K and D614G. We generated lentiviruses pseudotyped by the variant proteins and determined their resistance to neutralization by convalescent sera, vaccine-elicited antibodies and therapeutic monoclonal antibodies. Viruses with B.1.617 and B.1.618 spike were neutralized with a 2-5-fold decrease in titer by convalescent sera and vaccine-elicited antibodies. The E484Q and E484K versions were neutralized with a 2-4-fold decrease in titer. Virus with the B.1.617 spike protein was neutralized with a 4.7-fold decrease in titer by the Regeneron monoclonal antibody cocktail as a result of the L452R mutation. The modest neutralization resistance of the variant spike proteins to vaccine elicited antibody suggests that current vaccines will remain protective against the B.1.617 and B.1.618 variants.

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The basis of a more contagious 501Y.V1 variant of SARS-CoV-2

Cited by 143 publications

References 10 publications

The Spike of Concern—The Novel Variants of SARS-CoV-2

The Spike of Concern—The Novel Variants of SARS-CoV-2

SARS-CoV-2 Infectivity and Severity of COVID-19 According to SARS-CoV-2 Variants: Current Evidence

The Spike Proteins of SARS-CoV-2 B.1.617 and B.1.618 Variants Identified in India Provide Partial Resistance to Vaccine-elicited and Therapeutic Monoclonal Antibodies

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