E156G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.617.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape
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Abstract
Emerging variants of SARS-CoV-2 with better immune escape mechanisms and higher transmissibility remains a persistent threat across the globe. B.1.617.2 (Delta) variant was first emerged from Maharashtra, India in December, 2020. This variant is classified to be a major cause and concern of the second wave of COVID-19 in India. In the present study, we explored the genomic and structural basis of this variant through computational analysis, protein modelling and molecular dynamics (MD) simulations approach. B.1.617.2 variant carried E156G and Arg158, Phe-157/del mutations in NTD of spike protein. These mutations in N-terminal domain (NTD) of spike protein of B.1.617.2 variant revealed more rigidity and reduced flexibility compared to spike protein of Wuhan isolate. Further, docking and MD simulation study with 4A8 monoclonal antibody which was reported to bind NTD of spike protein suggested reduced binding of B.1.617.2 spike protein compared to that of spike protein of Wuhan isolate. The results of the present study demonstrate the possible case of immune escape and thereby fitness advantage of the new variant and further warrants demonstration through experimental evidence. Our study identified the probable mechanism through which B.1.617.2 variant is more pathogenically evolved with higher transmissibility as compared to the wild-type.
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SciScore for 10.1101/2021.06.07.447321: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources For binding residues (as shown in figure 2A) detection among both receptor (spike) and ligand (antibody-4A8) attraction forces were applied with <3Å cut off. antibody-4A8suggested: NoneSoftware and Algorithms Sentences Resources Mutated spike from SARS-CoV-2 used in this study were derived from amino acid sequence submitted in GAISAD with accession number EPI_ISL_2001211. GAISADsuggested: NoneMissing side chains were added through PRIME and pKa refinement was done with epik [17]. PRIMEsuggested: (Prime, RRID:SCR_014887)PYMOL was used for obtaining high resolution images [24]. PYMOLsuggested: (PyMOL, RRID:SCR_…SciScore for 10.1101/2021.06.07.447321: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources For binding residues (as shown in figure 2A) detection among both receptor (spike) and ligand (antibody-4A8) attraction forces were applied with <3Å cut off. antibody-4A8suggested: NoneSoftware and Algorithms Sentences Resources Mutated spike from SARS-CoV-2 used in this study were derived from amino acid sequence submitted in GAISAD with accession number EPI_ISL_2001211. GAISADsuggested: NoneMissing side chains were added through PRIME and pKa refinement was done with epik [17]. PRIMEsuggested: (Prime, RRID:SCR_014887)PYMOL was used for obtaining high resolution images [24]. PYMOLsuggested: (PyMOL, RRID:SCR_000305)DCCM and PCA both were analyzed using Schrodinger 2021-1 implemented python script run trj_essential_dynamics.py script of Desmond [18]. pythonsuggested: (IPython, RRID:SCR_001658)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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