Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

Gupta, Deepali; Sharma, Priyanka; Singh, Mahender; Kumar, Mukesh; Ethayathulla, A.S.; Kaur, Punit

doi:10.1007/s00018-021-04008-0

Cited by 49 publications

(61 citation statements)

References 157 publications

(197 reference statements)

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“…Important characteristic features of these mutations are also illustrated Sl. No Known mutations for other SARS-CoV-2 variants which present in Omicron Characteristics of mutations Reference 1 N501Y Augmenting the binding capability of S-protein with the ACE2 receptor also increased viral transmission The mutations N501Y and Q498R combination significantly increased the ACE2 binding affinity [ 48 , 49 ] 2 D614G High infectivity rate with greater binding affinity of S-protein to the ACE2 receptor Mutation added viral fitness to augment viral replication and transmission [ 50 , 51 ] 3 H655Y Mutation in the proximal part of the furin cleavage site could increase the spike cleavage and accelerate the transmission [ 52 ] 4 N679K Boost up the spike cleavage pattern and significantly increase the viral transmission [ 53 ] 5 P681H Mutation results in a conformational change to enhance the binding affinity of furin to S-protein and support entry of virus within host cells, also increasing the infectivity Such mutation (P681H) found in Alpha variant, in Delta, is shown as alternate mutation (P681R) [ 54 ] …”

Section: Resultsmentioning

confidence: 99%

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

et al. 2022

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The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00532-4.

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Section: Resultsmentioning

confidence: 99%

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

et al. 2022

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“…Also, patients infected with N501Y-harboring SARS-CoV-2 variants [namely, Alpha (B.1.1.7),Beta (B.1.351), and Gamma (P.1) variants] were less likely to be hospitalized than those infected with the Marseille-4 variant and with viruses of Nextstrain clade 20A that circulated between February and May 2020 in Marseille (Dao et al, 2021). SARS-CoV-2 genomic surveillance can also provide insights for phenotypic, structural and functional investigations of mutations and variants, as has been already broadly performed (Dong et al, 2021;Fantini et al, 2021;Gupta et al, 2021;Jaafar et al, 2021;Rahman et al, 2021). Particularly, SARS-CoV-2 mutation patterns in the spike protein may affect binding of neutralizing antibodies or T-cell recognition.…”

Section: Discussionmentioning

confidence: 99%

Analysis of SARS-CoV-2 Variants From 24,181 Patients Exemplifies the Role of Globalization and Zoonosis in Pandemics

et al. 2022

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After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.

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“…The S1 is the most immunodominant viral protein, with anti-RBD accounting for almost 90% of the neutralizing antibodies in COVID-19 convalescent plasma. In addition, an antigenic “supersite” was identified in NTD, which is a prominent target for antibody response ( 9 , 16 , 17 ). Interestingly, NTD was found to interact with tyrosine-protein kinase receptor UFO (AXL) highly expressed on pulmonary and bronchial cells, indicating a probable co-receptor involved in viral attachment and entry ( 18 ).…”

Section: Variations In Sars-cov-2 Genome and Proteomementioning

confidence: 99%

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Thakur¹,

Sasi²,

et al. 2022

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With the high rate of COVID-19 infections worldwide, the emergence of SARS-CoV-2 variants was inevitable. Several mutations have been identified in the SARS-CoV-2 genome, with the spike protein as one of the mutational hot spots. Specific amino acid substitutions such as D614G and N501Y were found to alter the transmissibility and virulence of the virus. The WHO has classified the variants identified with fitness-enhancing mutations as variants of concern (VOC), variants of interest (VOI) or variants under monitoring (VUM). The VOCs pose an imminent threat as they exhibit higher transmissibility, disease severity and ability to evade vaccine-induced and natural immunity. Here we review the mutational landscape on the SARS-CoV-2 structural and non-structural proteins and their impact on diagnostics, therapeutics and vaccines. We also look at the effectiveness of approved vaccines, antibody therapy and convalescent plasma on the currently prevalent VOCs, which are B.1.17, B.1.351, P.1, B.1.617.2 and B.1.1.529. We further discuss the possible factors influencing mutation rates and future directions.

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Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

Cited by 49 publications

References 157 publications

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

Analysis of SARS-CoV-2 Variants From 24,181 Patients Exemplifies the Role of Globalization and Zoonosis in Pandemics

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

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