Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2

Zhou, Xiaojuan; Ma, Fengge; Xie, Jun; Yuan, Meng; Li, Yunqiao; Shaabani, Namir; Zhao, Fangzhu; Huang, Deli; Wu, Nicholas C.; Lee, Chang-Chun David; Liu, Hejun; Li, Jiali; Chen, Zhonghui; Hong, Yazhen; Liu, Wen Hsien; Xiao, Nengming; Burton, Dennis R.; Tu, Haijian; Li, Hang; Chen, Xin; Teijaro, John R.; Wilson, Ian A.; Xiao, Changchun; Huang, Zhenguo

doi:10.1016/j.celrep.2021.109109

Cited by 27 publications

(30 citation statements)

References 79 publications

(111 reference statements)

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“…Neutralizing antibodies mainly target the RBD and NTD of spike ( 9 , 16 , 17 ). Previous studies have shown that the levels of antibodies against different forms of spike (including S1, S1/S2, and RBD) correlate well with the neutralization capacity of the samples ( 27 – 32 ).…”

Section: Resultsmentioning

confidence: 99%

“…Over the course of the COVID-19 pandemic, our understanding of the antibody response against SARS-CoV-2 has evolved considerably. Initial investigations suggested that most neutralizing antibodies elicited by infection or vaccination target the RBD ( 9 , 41 ). More recent studies have shown a codominance of antibodies that target the RBD and NTD ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…Spike is highly immunogenic in humans and, in infected and vaccinated individuals, readily elicits antibodies that play a critical role in protection ( 7 , 8 ). Most neutralizing antibodies isolated to date target the receptor-binding domain (RBD) on the S1 subunit ( 9 – 15 ). In addition, multiple neutralizing antibodies that target the N-terminal domain (NTD) of S1 have been isolated ( 16 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

et al. 2022

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“…However, severe ALI occurred in mice by adapting the virus to mouse ACE2 receptor and inserting the human ACE2 gene. Zhou et al [ 42 ] found that coronavirus entered the host cells by utilizing the spike protein to bind the hydrophobic pocket of the ACE2 extracellular catalytic domain. Once infected by the virus, ACE2 was downregulated in the cell and thus led to a dysregulation of the ACE2/Ang- (1-7)/MasR axis and the ACE/Ang II/AT1R axis [ 43 ].…”

Section: Ace2 and Covid-19mentioning

confidence: 99%

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Chen

Yin

et al. 2021

IJMS

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Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

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“…The key to vaccine-induced immunity is the ability of the induced antibodies to specifically bind to the SARS-CoV-2 with a strong binding affinity. The complex structures of the antibodies bound to the SARS-CoV-2 S RBD have been experimentally determined by using cryo-electron microscopy (cryo-EM) and X-ray diffraction [12,[16][17][18][19][20][21][22][23][24][25][26][27][28]. In the intracellular environment and in an extracellular medium, protein-protein docking is usually a spontaneous contact of high specificity established between two or more specific protein molecules; erroneous protein-protein docking rarely occurs [29].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Variants, RBD Mutations, Binding Affinity, and Antibody Escape

Yang

Guo

et al. 2021

IJMS

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Since 2020, the receptor-binding domain (RBD) of the spike protein of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been constantly mutating, producing most of the notable missense mutations in the context of “variants of concern”, probably in response to the vaccine-driven alteration of immune profiles of the human population. The Delta variant, in particular, has become the most prevalent variant of the epidemic, and it is spreading in countries with the highest vaccination rates, causing the world to face the risk of a new wave of the contagion. Understanding the physical mechanism responsible for the mutation-induced changes in the RBD’s binding affinity, its transmissibility, and its capacity to escape vaccine-induced immunity is the “urgent challenge” in the development of preventive measures, vaccines, and therapeutic antibodies against the coronavirus disease 2019 (COVID-19) pandemic. In this study, entropy–enthalpy compensation and the Gibbs free energy change were used to analyze the impact of the RBD mutations on the binding affinity of SARS-CoV-2 variants with the receptor angiotensin converting enzyme 2 (ACE2) and existing antibodies. Through the analysis, we found that the existing mutations have already covered almost all possible detrimental mutations that could result in an increase of transmissibility, and that a possible mutation in amino-acid position 498 of the RBD can potentially enhance its binding affinity. A new calculation method for the binding energies of protein–protein complexes is proposed based on the entropy–enthalpy compensation rule. All known structures of RBD–antibody complexes and the RBD–ACE2 complex comply with the entropy–enthalpy compensation rule in providing the driving force behind the spontaneous protein–protein docking. The variant-induced risk of breakthrough infections in vaccinated people is attributed to the L452R mutation’s reduction of the binding affinity of many antibodies. Mutations reversing the hydrophobic or hydrophilic performance of residues in the spike RBD potentially cause breakthrough infections of coronaviruses due to the changes in geometric complementarity in the entropy–enthalpy compensations between antibodies and the virus at the binding sites.

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Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2

Cited by 27 publications

References 79 publications

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

SARS-CoV-2 Variants, RBD Mutations, Binding Affinity, and Antibody Escape

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