Dataset Information

Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion.

ABSTRACT: Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge the immune system as it is found that neutralizing antibodies from prior infections or vaccines are less receptive to binding with the Delta spike protein. Here, we investigated the structural changes caused by the mutations in the Delta variant's receptor-binding interface and explored the effects on binding with the ACE2 receptor as well as with neutralizing antibodies. We find that the receptor-binding β-loop-β motif adopts an altered but stable conformation causing separation in some of the antibody binding epitopes. Our study shows reduced binding of neutralizing antibodies and provides a possible mechanism for the immune evasion exhibited by the Delta variant.

SUBMITTER: Baral P

PROVIDER: S-EPMC8364676 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion.

Baral Prabin P Bhattarai Nisha N Hossen Md Lokman ML Stebliankin Vitalii V Gerstman Bernard S BS Narasimhan Giri G Chapagain Prem P PP

Biochemical and biophysical research communications 20210815

Following the initial surges of the Alpha (B.1.1.7) and the Beta (B.1.351) variants, a more infectious Delta variant (B.1.617.2) is now surging, further deepening the health crises caused by the pandemic. The sharp rise in cases attributed to the Delta variant has made it especially disturbing and is a variant of concern. Fortunately, current vaccines offer protection against known variants of concern, including the Delta variant. However, the Delta variant has exhibited some ability to dodge th ...[more]

PMID: 34425281

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Project description:ImportanceThe Delta variant (B.1.617.2) is estimated to be more transmissible than previous strains of SARS-CoV-2, especially among children and adolescents. However, to our knowledge, there are no reports confirming this to date.ObjectiveTo gain a better understanding of the association of age with susceptibility to the Delta variant of SARS-CoV-2.Design, setting, and participantsThis decision analytic model used an age-structured compartmental model using the terms symptom onset (S), exposure (E), infectious (I), and quarantine (Q) (SEIQ) to estimate the age-specific force of infection, combining age-specific contact matrices and observed distribution of periods between each stage of infection (E to I [ie, latent period], I given S, and S to Q [ie, diagnostic delay]) developed in a previous contact tracing study. A bayesian inference method was used to estimate the age-specific force of infection (S to E) and, accordingly, age-specific susceptibility. The age-specific susceptibility during the third wave (ie, before Delta, from October 15 to December 22, 2020, when the COVID-19 vaccination campaign was not yet launched) and the fourth wave (ie, the Delta-driven wave, from June 27 to August 21, 2021) in Korea were compared. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta variant. This nationwide epidemiologic study included individuals who were diagnosed with COVID-19 during the study period in Korea. Data were analyzed from September to November 2021.ExposuresAge group during the third wave (ie, before Delta) and fourth wave (ie, Delta-driven) of the COVID-19 pandemic in South Korea.Main outcomes and measuresAge-specific susceptibility during the third and fourth waves was estimated.ResultsAmong 106 866 confirmed COVID-19 infections (including 26 597 infections and 80 269 infections during the third and fourth waves of COVID-19 in Korea, respectively), a significant difference in age-specific susceptibility to the Delta vs pre-Delta variant was found in the younger age group. After adjustment for contact pattern and vaccination status, the increase in susceptibility to the Delta vs pre-Delta variant was estimated to be highest in the group aged 10 to 15 years, approximately doubling (1.92-fold increase [95% CI, 1.86-fold to 1.98-fold]), whereas in the group aged 50 years or more, susceptibility to the Delta vs pre-Delta variant remained stable at an approximately 1-fold change (eg, among individuals aged 50-55 years: 0.997-fold [95% CI, 0.989-fold to 1.001-fold).Conclusions and relevanceIn this study, the Delta variant of SARS-CoV-2 was estimated to propagate more easily among children and adolescents than pre-Delta strains, even after adjusting for contact pattern and vaccination status.

Project description:The emergence of the B.1.617.2 (Delta) variant of the severe acute syndrome coronavirus (SARS-CoV-2) that emerged in 2019 (COVID-19), resulted in a surge of cases in India and has expanded and been detected across the world, including in the United States. The B.1.617.2 (Delta) variant has been seen to be twice more transmissible coupled with potential increases in disease severity and immune escape. As a result, case numbers and hospitalisations are once again on the rise in the USA. On 16 July 2021, the Centers for Disease Control and Prevention (CDC) reported a 7-day average 69.3% increase in new cases and a 35% increase in hospitalisations. Although the gold standard for SARS-CoV-2 variants identification remains genomic sequencing, this approach is not accessible to many clinical laboratories. The main goal of this study was to validate and implement the detection of the B.1.617.2 (Delta) variant utilising an open reverse transcription polymerase chain reaction (RT-PCR) platform by explicitly detecting the S-gene target failure (SGTF) corresponding to the deletion of two amino acids (ΔE156/ΔF157) characteristic of B.1.617.2 (Delta) variant. This approach was conceived as a rapid screening of B.1.617.2 (Delta) variant in conjunction with CDC's recommended N1 (nucleocapsid gene), N2, and RP (human RNase P) genes, as a pre-screening tool prior to viral genomic sequencing. We assessed 4,937 samples from 5 July to 5 September 2021. We identified the B.1.617.2 (Delta) variant in 435 of 495 positive samples (87.8%); the additional positive samples (7 samples, 1.4%) were found to belong to the B.1.1.7 (Alpha, UK) lineage and the remaining 53 samples (10.7%) were reported as 'other' lineages. Whole genome sequencing of 46 randomly selected samples validated the strains identified as positive and negative for the B.1.617.2 (Delta) variant and confirmed the S gene deletion in addition to B.1.617.2 characteristic mutations including L452R, T478K, P681R and D950N located in the spike protein. This modality has been used as routine testing at the Riverside University System Health (RUHS) Medical Center as a method for detection of B.1.617.2 (Delta) to pre-screen samples before genome sequencing. The assay can be easily implemented in clinical laboratories, most notably those with limited economic resources and access to genomic platforms.

Dataset Information

Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion.

Publications

Mutation-induced changes in the receptor-binding interface of the SARS-CoV-2 Delta variant B.1.617.2 and implications for immune evasion.

Similar Datasets

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