Pierce into Structural Changes of Interactions Between Mutated Spike Glycoproteins and ACE2 to Evaluate Its Potential Biological and Therapeutic Consequences

Hashemi, Zahra Sadat; Zarei, Mahboubeh; Mubarak, Shaden M.H.; Hessami, Anahita; Mard-Soltani, Maysam; Khalesi, Bahman; Zakeri, Alireza; Rahbar, Mahtab; Jahangiri, Abolfazl; Pourzardosht, Navid; Khalili, Saeed

doi:10.1007/s10989-021-10346-1

Cited by 7 publications

(5 citation statements)

References 51 publications

(54 reference statements)

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“…Another example is the P681H mutation located in the furin protease cleavage site. This non‐conservative substitution (non‐polar amino acid to a positively charged polar amino acid) may result in more efficient spike protein cleavage 54 . The H655Y substitution is also found in the furin cleavage site.…”

Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

“…This non‐conservative substitution (non‐polar amino acid to a positively charged polar amino acid) may result in more efficient spike protein cleavage. 54 The H655Y substitution is also found in the furin cleavage site. While this mutation causes only a modest increase in the binding affinity to ACE2 (1.2‐fold), these mutations may account for the enhanced spread of the Omicron variant, through enhanced proteolytic cleavage.…”

Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

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SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

100

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New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin‐converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

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Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

100

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“…The A570D substitution was suggested to modulate the conformational transition of the RBD between its open and closed state 43 . The P681H substitution contributed to an increased central cavity, causing the mutated protein to be less compact 44 . The location of the D1118H substitution was suggested to potentially have an impact on the trimer assembly structure, stability, or dynamics 45 .…”

Section: Resultsmentioning

confidence: 99%

In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design

Huang,

Chen,

Lin

et al. 2023

Sci Rep

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The COVID-19 pandemic has had a widespread impact on a global scale, and the evolution of considerable dominants has already taken place. Some variants contained certain key mutations located on the receptor binding domain (RBD) of spike protein, such as E484K and N501Y. It is increasingly worrying that these variants could impair the efficacy of current vaccines or therapies. Therefore, analyzing and predicting the high-risk mutations of SARS-CoV-2 spike glycoprotein is crucial to design future vaccines against the different variants. In this work, we proposed an in silico approach, immune-escaping score (IES), to predict high-risk immune-escaping hot spots on the receptor-binding domain (RBD), implemented through integrated delta binding free energy measured by computational mutagenesis of spike-antibody complexes and mutation frequency calculated from viral genome sequencing data. We identified 23 potentially immune-escaping mutations on the RBD by using IES, nine of which occurred in omicron variants (R346K, K417N, N440K, L452Q, L452R, S477N, T478K, F490S, and N501Y), despite our dataset being curated before the omicron first appeared. The highest immune-escaping score (IES = 1) was found for E484K, which agrees with recent studies stating that the mutation significantly reduced the efficacy of neutralization antibodies. Furthermore, our predicted delta binding free energy and IES show a high correlation with high-throughput deep mutational scanning data (Pearson’s r = 0.70) and experimentally measured neutralization titers data (mean Pearson’s r = −0.80). In summary, our work presents a new method to identify the potentially immune-escaping mutations on the RBD and provides valuable insights into future COVID-19 vaccine design.

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“…The A570D substitution was suggested to modulate the conformational transition of the RBD between its open and closed state 27 . The P681H substitution contributed to an increased central cavity, causing the mutated protein to be less compact 28 . The location of the D1118H substitution was suggested to potentially have an impact on the trimer assembly structure, stability, or dynamics 29 .…”

Section: Mutation Frequency Analysis For High-risk Hot Spots Identifi...mentioning

confidence: 99%

In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design

Huang¹,

Chen²,

Lin³

et al. 2023

Preprint

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The COVID-19 pandemic has had a widespread impact on a global scale, and the evolution of considerable dominants has already taken place. Some variants contained certain key mutations located on the receptor binding domain (RBD) of spike protein, such as E484K and N501Y. It is increasingly worrying that these variants could impair the efficacy of current vaccines or therapies. Therefore, how to design future vaccines to prevent the different variants remains urgent. In this work, we proposed an in silico approach, in which we combined binding free energy measured by computational mutagenesis of spike-antibody complexes and mutation frequency calculated from viral genome sequencing data, to estimate an immune-escaping score (IES) and predict immune-escaping hot spots. We identified 23 immune-escaping mutations on the RBD, nine of which occurred in omicron variants (R346K, K417N, N440K, L452Q, L452R, S477N, T478K, F490S, and N501Y), despite our dataset being curated before the omicron first appeared. The highest immune-escaping score (IES=1) was found for E484K, which agrees with recent studies stating that the mutation significantly reduced the efficacy of neutralization antibodies. Furthermore, our predicted binding free energy and IES show a high correlation with high-throughput deep mutational scanning (Pearson’s r = 0.70) and experimentally measured neutralization titers data (mean Pearson’s r = -0.80). In summary, our work provides valuable insights and will help design future COVID-19 vaccines.

show abstract

Pierce into Structural Changes of Interactions Between Mutated Spike Glycoproteins and ACE2 to Evaluate Its Potential Biological and Therapeutic Consequences

Cited by 7 publications

References 51 publications

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design

In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design

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