Surface electrostatic shift on spike protein decreased antibody activities against SARS-CoV-2 Omicron variant

Yuan, Shu; Jiang, Si‐Cong; Zhang, Zhongwei; Fu, Yu‐Fan; Yang, Xin-Yue; Li, Zi-Lin; Hu, Jing; Du, Junbo; Yuan, Ming; Chen, Yang-Er

doi:10.1016/j.jinf.2022.04.033

Cited by 6 publications

(7 citation statements)

References 11 publications

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“…A large number of papers have shown that electrostatic interactions are indeed very important for SARS-CoV-2 (e.g., refs , , , and − ). Most of the studies have focused on the interactions involving the receptor-binding domain (RBD) of the SARS-CoV-2 spike homotrimer glycoprotein due to its biological central relevance.…”

Section: Introductionmentioning

confidence: 99%

Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

2022

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Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein–protein systems under different physical–chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pK a s for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This “RBD charge rule” should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.

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Section: Introductionmentioning

confidence: 99%

Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

2022

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“…refs. [23][24][25][26][27][28][29][30][31][32][33][34][35][36] ). Most of the studies have focused on the interactions involving the receptor-binding domain (RBD) of the SARS-CoV-2 spike homotrimer glycoprotein due to its biological central relevance.…”

Section: Introductionmentioning

confidence: 99%

Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge-rule

Silva

Giron

Laaksonen

2022

Preprint

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Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein-protein systems under different physical-chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pKas for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This RBD charge rule should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.

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“…To verify this hypothesis, we designed four sets of mixed vaccines for SARS-CoV-2. In our previous paper, 21 predicted epitopes for the SARS-CoV-2 spike (S) protein were screened out 14 . Among them, only one epitope "YRLFRKSN", with surface accessible scores > 2.0 was found in the receptor binding domain (RBD) region, which was also the Nterminus of the binding sequence to the human neutralizing monoclonal antibody CV30 15,16 and named as epitope #A (Fig.…”

Section: High-titer and Longer-lasting Vaccines Against Sars-cov-2mentioning

confidence: 99%

“…The other eight epitopes outside of the RBD region with surface accessible scores 17 > 2.0 were named as epitopes #B to #I. Moreover, all these epitopes were selected for another reason, -that is, they are all conserved in all SARS-CoV-2 variants (from the original strain to Omicron) 14 . Polyclonal antibodies against SARS-CoV-2 S protein were raised in rabbits by using keyhole limpet hemocyanin (KLH)-conjugated peptides as the antigens 18 .…”

Section: High-titer and Longer-lasting Vaccines Against Sars-cov-2mentioning

confidence: 99%

“…Compared with the original strain, the antibody titers of all four groups declined by 38%-46% when binding with Omicron S protein. The decline in antibody titer against the Omicron may be attributed to a change in surface charge of the S protein 14,19 . For the original virus strain, the antibody titers of Groups 2, 3, and 4 increased by 1.44, 2.35, and 4.24 times, respectively, compared to Group 1 (Fig.…”

Section: High-titer and Longer-lasting Vaccines Against Sars-cov-2mentioning

confidence: 99%

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The number of similar epitopes determines the longevity of immunological memory

Yuan

Yang

et al. 2023

Preprint

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The half-life of specific antibodies against various antigens varies tremendously from a few months to over 10,000 years. The reasons are largely unknown. Through epitope analysis of representative viruses, we found that the longevity of immunological memory may be correlated with the number of epitopes with similar sequences (EWSS) within each virus. Accordingly, a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 4.5-times higher antibody titers and over 100 months of half-life was developed in a rabbit model. The decay pattern of antibodies against each epitope or the entire SARS-CoV-2 spike protein was roughly correlated with the number of EWSS in immunizationtreatments, –that is, for every additional EWSS, the half-life of the antibody would be doubled. After immunization, proportions of antigen-specific memory B cells (MBC) first increased and then decreased. In the descending phase, the antibody titers were positively correlated with the numbers of MBC. This study also discusses improvement measures for vaccines against other viruses.

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Surface electrostatic shift on spike protein decreased antibody activities against SARS-CoV-2 Omicron variant

Cited by 6 publications

References 11 publications

Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule

Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge-rule

The number of similar epitopes determines the longevity of immunological memory

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