A systematic study on the binding affinity of SARS-CoV-2 spike protein to antibodies

An, Ke; Zhu, Xiaohong; Yan, Junfang; Xu, Peiyi; Hu, Linfeng; Bai, Chen

doi:10.3934/microbiol.2022038

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…This result aligned with previous studies that described considerably reduced humoral responses against the Omicron strain and almost no vaccine effectiveness against symptomatic disease after two doses of BNT162b2 [39]. Omicron sub-variants have generally higher immune escape ability than other SARS-CoV-2 VOCs [35,40], even though the earlier Omicron sub-variants (BA.1 and BA.2) appeared to have stronger binding affinities than other VOCs [40]. The Omicron variant is characterized by great antigenic variability due to the selection of 37 mutations in the spike protein, the main immunogenic protein of the virus, and it is capable of inducing the production of neutralizing antibodies [41,42].…”

Section: Discussionsupporting

confidence: 91%

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2

Immordino,

Pisciotta,

Amodio

et al. 2023

Vaccines

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Although the anti-COVID-19 vaccination has proved to be an effective preventive tool, “breakthrough infections” have been documented in patients with complete primary vaccination courses. Most of the SARS-CoV-2 neutralizing antibodies produced after SARS-CoV-2 infection target the spike protein receptor-binding domain which has an important role in facilitating viral entry and the infection of the host cells. SARS-CoV-2 has demonstrated the ability to evolve by accumulating mutations in the spike protein to escape the humoral response of a host. The aim of this study was to compare the titers of neutralizing antibodies (NtAbs) against the variants of SARS-CoV-2 by analyzing the sera of recovered and vaccinated healthcare workers (HCWs). A total of 293 HCWs were enrolled and divided into three cohorts as follows: 91 who had recovered from SARS-CoV-2 infection (nVP); 102 that were vaccinated and became positive after the primary cycle (VP); and 100 that were vaccinated with complete primary cycles and concluded the follow-up period without becoming positive (VN). Higher neutralization titers were observed in the vaccinated subjects’ arms compared to the nVP subjects’ arms. Differences in neutralization titers between arms for single variants were statistically highly significant (p < 0.001), except for the differences between titers against the Alpha variant in the nVP and in VP groups, which were also statistically significant (p < 0.05). Within the nVP group, the number of subjects with an absence of neutralizing antibodies was high. The presence of higher titers in patients with a complete primary cycle compared to patients who had recovered from infection suggested the better efficacy of artificial immunization compared to natural immunization, and this further encourages the promotion of vaccination even in subjects with previous infections.

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Section: Discussionsupporting

confidence: 91%

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2

Immordino,

Pisciotta,

Amodio

et al. 2023

Vaccines

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“…The ΔΔ G of BA.3 to antibodies CT‐P59, AZD1061, and LY‐CoV555 is more positive than that of BA.1 (Table S3), indicating greater interference with the spike/antibody interactions and possible stronger immune evasion. BA.4 exhibits a stronger spike/antibody affinity reduction effect than the other three sublineages (Table S3) implying it may have the strongest immune evasion ability 77 . These analyses suggested that, in addition to gaining strong ACE2 affinity, the omicron variant has larger immune evasion ability to further enhance its transmission ability.…”

Section: Resultsmentioning

confidence: 92%

“…BA.4 exhibits a stronger spike/antibody affinity reduction effect than the other three sublineages (Table S3) implying it may have the strongest immune evasion ability. 77 These analyses suggested that, in addition to gaining strong ACE2 affinity, the omicron variant has larger immune evasion ability to further enhance its transmission ability.…”

Section: Weaker Affinities To Most Antibodiesmentioning

confidence: 99%

Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant

An,

Yang,

Luo

et al. 2024

Proteins

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The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID‐19 pandemic. In order to investigate the relationship between these mutations and the variant's high transmissibility, we conducted a systematic analysis of the mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions and explored the structural/energy correlation of key mutations, utilizing a reliable coarse‐grained model. Our study extended beyond the receptor‐binding domain (RBD) of spike trimer through comprehensive modeling of the full‐length spike trimer rather than just the RBD. Our free‐energy calculation revealed that the enhanced binding affinity between the spike protein and the ACE2 receptor is correlated with the increased structural stability of the isolated spike protein, thus explaining the omicron variant's heightened transmissibility. The conclusion was supported by our experimental analyses involving the expression and purification of the full‐length spike trimer. Furthermore, the energy decomposition analysis established those electrostatic interactions make major contributions to this effect. We categorized the mutations into four groups and established an analytical framework that can be employed in studying future mutations. Additionally, our calculations rationalized the reduced affinity of the omicron variant towards most available therapeutic neutralizing antibodies, when compared with the wild type. By providing concrete experimental data and offering a solid explanation, this study contributes to a better understanding of the relationship between theories and observations and lays the foundation for future investigations.

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“…This CG model is designed to characterize protein stabilities and conformational energies, which also enhances the model’s electrostatic properties ( 31 ), and has been refined specially for the analysis of membrane protein ( 32 ). Furthermore, the CG model has been extensively employed to investigate the molecular mechanism of biological functions in a broad array of complex systems, like ATPase ( 33 – 35 ), GPCRs ( 36 – 38 ), Hv1 channel ( 39 ), and SARS-Cov2 spike protein ( 40 – 43 ). Its extensive application has affirmed it as a reliable tool to depict the energy landscapes during the conformational transitions of proteins.…”

mentioning

confidence: 99%

Exploring the activation mechanism of metabotropic glutamate receptor 2

Zhu,

Luo,

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Homomeric dimerization of metabotropic glutamate receptors (mGlus) is essential for the modulation of their functions and represents a promising avenue for the development of novel therapeutic approaches to address central nervous system diseases. Yet, the scarcity of detailed molecular and energetic data on mGlu2 impedes our in-depth comprehension of their activation process. Here, we employ computational simulation methods to elucidate the activation process and key events associated with the mGlu2, including a detailed analysis of its conformational transitions, the binding of agonists, G i protein coupling, and the guanosine diphosphate (GDP) release. Our results demonstrate that the activation of mGlu2 is a stepwise process and several energy barriers need to be overcome. Moreover, we also identify the rate-determining step of the mGlu2’s transition from the agonist-bound state to its active state. From the perspective of free-energy analysis, we find that the conformational dynamics of mGlu2’s subunit follow coupled rather than discrete, independent actions. Asymmetric dimerization is critical for receptor activation. Our calculation results are consistent with the observation of cross-linking and fluorescent-labeled blot experiments, thus illustrating the reliability of our calculations. Besides, we also identify potential key residues in the G i protein binding position on mGlu2, mGlu2 dimer’s TM6–TM6 interface, and Gi α5 helix by the change of energy barriers after mutation. The implications of our findings could lead to a more comprehensive grasp of class C G protein-coupled receptor activation.

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A systematic study on the binding affinity of SARS-CoV-2 spike protein to antibodies

Cited by 6 publications

References 57 publications

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2

An Analysis of the Neutralizing Antibodies against the Main SARS-CoV-2 Variants in Healthcare Workers (HCWs) Vaccinated against or Infected by SARS-CoV-2

Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant

Exploring the activation mechanism of metabotropic glutamate receptor 2

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