Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among <scp>SARS‐CoV</scp>‐2 variants of concern

Kim, Seonghan; Liu, Yi; Ziarnik, Matthew; Seo, Sangjae; Cao, Yiwei; Zhang, X Frank; Im, Wonpil

doi:10.1002/jcc.27025

Cited by 39 publications

(36 citation statements)

References 54 publications

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“…Additionally, the P681R mutation found in the Delta S and Omicron BA.1 S has been found to increase pathogenicity and proteolytic processing ( Liu et al, 2022b ; Saito et al, 2021 ), and RBD mutations in variants of concern have been found to increase affinity for the ACE2 receptor ( Han et al, 2022 ; Ozono et al, 2021 ). Omicron shows the highest affinity for ACE2 among preceding variants, attributable to several mutations on the RBD ( Kim et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

Braet

Buckley

Venkatakrishnan

et al. 2023

eLife

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SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.

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Section: Introductionmentioning

confidence: 99%

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

Braet

Buckley

Venkatakrishnan

et al. 2023

eLife

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“…The consensus about the driving force behind S protein binding to HS is electrostatic interactions between the negatively charged HS and cluster of positive charges on the S-protein surface. 91 , 106 − 110 In a large-scale docking study with various glycocalyx components, Kim et al reported six novel docking sites in addition to supporting the previously proposed sites. 91 This study investigated the 12 800 binding poses of HS-based molecules on the S protein.…”

Section: Impact Of S-protein Glycansmentioning

confidence: 63%

Many Roles of Carbohydrates: A Computational Spotlight on the Coronavirus S Protein Binding

Maity

Acharya

2023

ACS Appl. Bio Mater.

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Glycosylation is one of the post-translational modifications with more than 50% of human proteins being glycosylated. The exact nature and chemical composition of glycans are inaccessible to X-ray or cryo-electron microscopy imaging techniques. Therefore, computational modeling studies and molecular dynamics must be used as a “computational microscope”. The spike (S) protein of SARS-CoV-2 is heavily glycosylated, and a few glycans play a more functional role “ beyond shielding ”. In this mini-review, we discuss computational investigations of the roles of specific S-protein and ACE2 glycans in the overall ACE2-S protein binding. We highlight different functions of specific glycans demonstrated in myriad computational models and simulations in the context of the SARS-CoV-2 virus binding to the receptor. We also discuss interactions between glycocalyx and the S protein, which may be utilized to design prophylactic polysaccharide-based therapeutics targeting the S protein. In addition, we underline the recent emergence of coronavirus variants and their impact on the S protein and its glycans.

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“…Furthermore, the vaccine candidate was able to generate Omicron variant binding and ACE2 blocking antibodies without specifically vaccinating with Omicron, suggesting the potential for broad protection against emerging variants. [56][57][58][59][60] This is particularly significant given the emergence of highly diverged SARS-CoV-2 variants, such as Omicron, which have raised concerns about vaccine efficacy and the need for updated vaccines. 56,58,59,61 Another significant feature of the vaccine candidate is its tetravalent composition, which targets the spike proteins of four different SARS-CoV-2 variants.…”

Section: Discussionmentioning

confidence: 99%

Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers

Khan

Kim

Hingrat

et al. 2023

Preprint

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The COVID-19 pandemic has highlighted the need for safe and effective vaccines to be rapidly developed and distributed worldwide, especially considering the emergence of new SARS-CoV-2 variants. Protein subunit vaccines have emerged as a promising approach due to their proven safety record and ability to elicit robust immune responses. In this study, we evaluated the immunogenicity and efficacy of an adjuvanted tetravalent S1 subunit protein COVID-19 vaccine candidate composed of the Wuhan, B.1.1.7 variant, B.1.351 variant, and P.1 variant spike proteins in a nonhuman primate model with controlled SIVsab infection. The vaccine candidate induced both humoral and cellular immune responses, with T- and B cell responses mainly peaking post-boost immunization. The vaccine also elicited neutralizing and cross-reactive antibodies, ACE2 blocking antibodies, and T-cell responses, including spike specific CD4+ T cells. Importantly, the vaccine candidate was able to generate Omicron variant spike binding and ACE2 blocking antibodies without specifically vaccinating with Omicron, suggesting potential broad protection against emerging variants. The tetravalent composition of the vaccine candidate has significant implications for COVID-19 vaccine development and implementation, providing broad antibody responses against numerous SARS-CoV-2 variants.

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Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among SARS‐CoV‐2 variants of concern

Cited by 39 publications

References 54 publications

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

Many Roles of Carbohydrates: A Computational Spotlight on the Coronavirus S Protein Binding

Tetravalent SARS-CoV-2 S1 Subunit Protein Vaccination Elicits Robust Humoral and Cellular Immune Responses in SIV-Infected Rhesus Macaque Controllers

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