SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of <i>Spike</i> Gene

Jhun, Hyunjhung; Park, Ho-Young; Hisham, Yasmin; Song, Chang‐Seon; Kim, Soohyun

doi:10.4110/in.2021.21.e32

Cited by 54 publications

(38 citation statements)

References 63 publications

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“…1.1.529)-technical-brief-and-priority-actions-for-member-states, accessed on 17 December 2021). Omicron has more than 30-residue mutations in the spike protein in comparison to 15-residue mutations in the Delta variant [1], which might be the reason for its enhanced transmissibility [2]. The kinds of vaccines approved have played great roles in controlling the spread of SARS-CoV-2 [3,4].…”

Section: Introductionmentioning

confidence: 99%

Steep Decline in Binding Capability of SARS-CoV-2 Omicron Variant (B.1.1.529) RBD to the Antibodies in Early COVID-19 Convalescent Sera and Inactivated Vaccine Sera

Zhou

et al. 2022

Viruses

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A new SARS-CoV-2 variant B.1.1.529 was named by the WHO as Omicron and classified as a Variant of Concern (VOC) on 26 November 2021. Because this variant has more than 50 mutations, including 30 mutations on the spike, it has generated a lot of concerns on the potential impacts of the VOC on COVID-19. Here through ELISA assays using the recombinant RBD proteins with sequences the same to that of SARS-CoV-2 WIV04 (lineage B.1), the Delta variant and the Omicron variant as the coating antigens, the binding capabilities between the RBDs and the antibodies in COVID-19 convalescent sera and vaccine sera after two doses of the inactivated vaccine produced by Sinopharm WIBP are compared with each other. The results showed that the Omicron variant may evade antibodies induced by the ancestral strain and by the inactivated vaccine, with significant reduction in the binding capability of its RBD much greater than that of the Delta variant.

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Section: Introductionmentioning

confidence: 99%

Steep Decline in Binding Capability of SARS-CoV-2 Omicron Variant (B.1.1.529) RBD to the Antibodies in Early COVID-19 Convalescent Sera and Inactivated Vaccine Sera

Zhou

et al. 2022

Viruses

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“…Although the Delta variant currently had a negligible effect on VE, a continued adaptation of SARS-CoV-2 to human transmission and immune escape seems inevitable. The Omicron variant is believed to pose a grave threat to humans because there are at least 32 amino acid mutations that occurred in spike protein, which is the target antigen for current COVID-19 vaccines, while the number of that for Delta is only 15 ( Jhun et al, 2021 ). The preliminary evidence suggested an increased risk of reinfection with this variant, as compared to other VOCs.…”

Section: What Factors Influence the Duration Of Protection?mentioning

confidence: 99%

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective

et al. 2022

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The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know; some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

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“…Within the receptor binding domain (RBD; aa319 to aa541) of the wild type (wt) SARS-CoV-2 spike protein, the amino acid sequence stretch aa437 to aa508 encompasses the receptor binding motif (RBM) [1]. Amino acid residue exchanges have been observed at distinct RBM positions with all variants of concern (VOCs) [2]. The newly reported Omicron VOC carries ten exchanged amino acids (Figure 1) in its RBM, of which four (K440, S446, K478, and A484) are also found in SARS-CoV-1-, in bat-, and/or in civet-derived RBMs at the respective positions and through which Omicron's RBM can be distinguished from that of SARS-CoV-2's wt [3].…”

Section: Amino Acid Sequence Alignments Point To a Shift In Rbm Chara...mentioning

confidence: 99%

“…This exchange in Omicron´s RBM was later corrected to R493. N479 of SARS-CoV-1´s RBM makes direct contact with hACE2 and is considered to be responsible In detail: residue K478 has been designated the decisive amino acid exchange in Delta's RBM [2]. K478 has been retained in Omicron, which, similar to residues K440, S446, and N477 (all three are rarely seen in other variants [9]), lends Omicron more "non-SARS-CoV-2 wt" characteristics, e.g., K478 matches with K465 in the RBM of SARS-CoV-1.…”

Section: Ntakqdqg-----qyyyrshrktklkpferdlssde-ngv-rt-ls-----------tyd...mentioning

confidence: 99%

From Free Binding Energy Calculations of SARS-CoV-2—Receptor Interactions to Cellular Immune Responses

2022

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Our study focuses on free energy calculations of SARS-CoV-2 spike protein receptor binding motives (RBMs) from wild type and variants of concern (VOCs), with emphasis on SARS-CoV-2 Omicron. Our computational analysis underlines the occurrence of positive selection processes that specify Omicron host adaption and bring changes on the molecular level into context with clinically relevant observations. Our free energy calculation studies regarding the interaction of Omicron’s RBM with human angiotensin converting enzyme 2 (hACE2) indicate weaker binding to the receptor than Alpha’s or Delta’s RBMs. Upon weaker binding, fewer viruses are predicted to be generated in time per infected cell, resulting in a delayed induction of danger signals as a trade-off. Along with delayed immunogenicity and pathogenicity, more viruses may be produced in the upper respiratory tract, explaining enhanced transmissibility. Since in interdependence on the human leukocyte antigen type (HLA type), more SARS-CoV-2 Omicron viruses are assumed to be required to initiate inflammatory immune responses, and because of pre-existing partial immunity through previous infections and/or vaccinations, which mostly guard the lower respiratory tract, overall disease severity is expected to be reduced.

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SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

Cited by 54 publications

References 63 publications

Steep Decline in Binding Capability of SARS-CoV-2 Omicron Variant (B.1.1.529) RBD to the Antibodies in Early COVID-19 Convalescent Sera and Inactivated Vaccine Sera

Steep Decline in Binding Capability of SARS-CoV-2 Omicron Variant (B.1.1.529) RBD to the Antibodies in Early COVID-19 Convalescent Sera and Inactivated Vaccine Sera

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective

From Free Binding Energy Calculations of SARS-CoV-2—Receptor Interactions to Cellular Immune Responses

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