Omicron Spike protein has a positive electrostatic surface that promotes ACE2 recognition and antibody escape

Gan, Hin Hark; Zinno, John; Piano, Fabio; Gunsalus, Kristin C.

doi:10.1101/2022.02.13.480261

Cited by 6 publications

(3 citation statements)

References 32 publications

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“…Thus, the effort of the scientific community has been mainly focused on the description of the most immunogenic regions of the Spike protein, and how the variant's amino acid substitutions can impact the binding with known antibodies. [52][53][54][55] A complete overview of the various antibody-spike complexes experimentally determined has been furnished in this recent paper, with particular attention to the epitope region the antibodies are bound to. 56 However, we focused on a different aspect.…”

Section: Sequence and Structural Analysis Of Anti-spike Antibodiesmentioning

confidence: 99%

Dynamical changes of SARS‐CoV‐2 spike variants in the highly immunogenic regions impact the viral antibodies escaping

et al. 2023

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The prolonged circulation of the SARS-CoV-2 virus resulted in the emergence of several viral variants, with different spreading features. Moreover, the increased number of recovered and/or vaccinated people introduced a selective pressure toward variants able to evade the immune system, developed against the former viral versions. This process results in reinfections. Aiming to study the latter process, we first collected a large structural dataset of antibodies in complex with the original version of SARS-CoV-2 Spike protein. We characterized the peculiarities of such antibodies population with respect to a control dataset of antibody-protein complexes, highlighting some statistically significant differences between these two sets of antibodies. Thus, moving our attention to the Spike side of the complexes, we identify the Spike region most prone to interaction with antibodies, describing in detail also the energetic mechanisms used by antibodies to recognize different epitopes. In this framework, fast protocols able to assess the effect of novel mutations on the cohort of developed antibodies would help establish the impact of the variants on the population. Performing a molecular dynamics simulation of the trimeric form of the SARS-CoV-2 Spike protein for the wild type and two variants of concern, that is, the Delta and Omicron variants, we described the physicochemical features and the conformational changes experienced locally by the variants with respect to the original version.Hence, combining the dynamical information with the structural study on the antibody-spike dataset, we quantitatively explain why the Omicron variant has a higher capability of escaping the immune system than the Delta variant, due to the higher conformational variability of the most immunogenic regions. Overall, our results shed light on the molecular mechanism behind the different responses the SARS-CoV-2 variants display against the immune response induced by either vaccines or previous infections. Moreover, our analysis proposes an approach that can be easily extended to both other SARS-CoV-2 variants or different molecular systems.

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Section: Sequence and Structural Analysis Of Anti-spike Antibodiesmentioning

confidence: 99%

Dynamical changes of SARS‐CoV‐2 spike variants in the highly immunogenic regions impact the viral antibodies escaping

et al. 2023

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“…Kumar et al ( 30 ) showed that Omicron and its subvariants have a higher affinity for human angiotensin-converting enzyme 2 (ACE2) compared with the wild type and Delta variants because of a significant number of mutations in the RBD, therefore, a potentially higher transmission rate ( 30 ). Computational analysis perform by Gan et al ( 31 ) showed that Omicron Spike trimer surface has transitioned to strongly positive electrostatic surface compared to Wuhan-Hu-1 variant. This result suggest that Omicron mutations not only enhance ACE2 recognition but also cause antibody escape ( 31 ).…”

Section: Omicron Genomicsmentioning

confidence: 99%

“…Computational analysis perform by Gan et al ( 31 ) showed that Omicron Spike trimer surface has transitioned to strongly positive electrostatic surface compared to Wuhan-Hu-1 variant. This result suggest that Omicron mutations not only enhance ACE2 recognition but also cause antibody escape ( 31 ). BA.2 and BA.3 have a higher transmission potential compared with the BA.1 and BA.1.1 ( 26 ).…”

Section: Omicron Genomicsmentioning

confidence: 99%

The Omicron variant of concern: The genomics, diagnostics, and clinical characteristics in children

et al. 2022

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Since WHO announced the COVID-19 pandemic in March 2020, SARS-CoV-2 has undergone several mutations, with the most recent variant first identified in South Africa in November 2021, the SARS-CoV-2 variant of concern (VOC B.1.1.529) named by WHO as Omicron. To date, it has undergone more mutations compared to previous SARS-CoV-2 variants, particularly, in the S gene that encodes the spike protein, which can cause S gene target failure in some PCR kits. Since its discovery, the Omicron variant has caused a sharp rise in COVID-19 cases worldwide and was responsible for a record of 15 million new COVID-19 cases reported globally in a single week, although this may be an underestimate. Since January 2022, Omicron subvariants with variable genetic characteristics, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.12.2 have been identified, with several countries reporting BA.1.1 was the major subvariant (27.42%), followed by BA.2 (25.19%). At the begining of May 2022, BA.2.12.1 mostly (42%) was detected in the United States. Like adults, the clinical manifestations of the Omicron variant in children are similar to the previous variants consisting of fever, cough, vomiting, breathing difficulties, and diarrhea, with some reports on croup-like symptoms and seizures. Though it presents apparently milder disease than the Delta variant, it is significantly more contagious and has caused more hospitalizations, especially in unvaccinated children younger than 5 years and unvaccinated or incompletely vaccinated adults. However, there is insufficient evidence yet to distinguish the Omicron variant from the other variants based solely on the clinical manifestations, therefore, this review presents a brief literature review of the most current evidence and data related to Omicron.

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Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference

Durmaz¹,

Köchl²,

Krassnigg³

et al. 2022

Sci Rep

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To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring.

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Omicron Spike protein has a positive electrostatic surface that promotes ACE2 recognition and antibody escape

Cited by 6 publications

References 32 publications

Dynamical changes of SARS‐CoV‐2 spike variants in the highly immunogenic regions impact the viral antibodies escaping

Dynamical changes of SARS‐CoV‐2 spike variants in the highly immunogenic regions impact the viral antibodies escaping

The Omicron variant of concern: The genomics, diagnostics, and clinical characteristics in children

Structural bioinformatics analysis of SARS-CoV-2 variants reveals higher hACE2 receptor binding affinity for Omicron B.1.1.529 spike RBD compared to wild type reference

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