The impact of mutations on the structural and functional properties of SARS-CoV-2 proteins: A comprehensive bioinformatics analysis
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Abstract
An in-depth analysis of first wave SARS-CoV-2 genome is required to identify various mutations that significantly affect viral fitness. In the present study, we have performed comprehensive in-silico mutational analysis of 3C-like protease (3CLpro), RNA dependent RNA polymerase (RdRp), and spike (S) proteins with the aim of gaining important insights into first wave virus mutations and their functional and structural impact on SARS-CoV-2 proteins. Our integrated analysis gathered 3465 SARS-CoV-2 sequences and identified 92 mutations in S, 37 in RdRp, and 11 in 3CLpro regions. The impact of those mutations was also investigated using various in silico approaches. Among these 32 mutations in S, 15 in RdRp, and 3 in 3CLpro proteins are found to be deleterious in nature and could alter the structural and functional behavior of the encoded proteins. D614G mutation in spike and P323L in RdRp are the globally dominant variants with a high frequency. Most of them have also been found in the binding moiety of the viral proteins which determine their critical involvement in the host-pathogen interactions and drug targets. The findings of the current study may facilitate better understanding of COVID-19 diagnostics, vaccines, and therapeutics.
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SciScore for 10.1101/2021.03.01.433340: (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
Software and Algorithms Sentences Resources Sequence alignment and mutation analysis: Protein sequences of S, RdRp and 3CLpro regions were first aligned with the reference sequence (NC_045512) using CLC workbench 7 and Bioedit [9]. Bioeditsuggested: (BioEdit, RRID:SCR_007361)Predicting the functional impact of mutations: To characterize mutations as neutral or deleterious to the structure and function of the encoded proteins, SIFT [10], PhD-SNP [11], and SNAP2 tools [12] were employed. PhD-SNPsuggested: (PhD-SNP, RRID:SCR_010782)SIFT predicts the functional importance of an amino acid variations based on the conservation and … SciScore for 10.1101/2021.03.01.433340: (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
Software and Algorithms Sentences Resources Sequence alignment and mutation analysis: Protein sequences of S, RdRp and 3CLpro regions were first aligned with the reference sequence (NC_045512) using CLC workbench 7 and Bioedit [9]. Bioeditsuggested: (BioEdit, RRID:SCR_007361)Predicting the functional impact of mutations: To characterize mutations as neutral or deleterious to the structure and function of the encoded proteins, SIFT [10], PhD-SNP [11], and SNAP2 tools [12] were employed. PhD-SNPsuggested: (PhD-SNP, RRID:SCR_010782)SIFT predicts the functional importance of an amino acid variations based on the conservation and alignment of highly similar orthologoue and paralogoue protein sequences. SIFTsuggested: (SIFT, RRID:SCR_012813)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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.
- No funding statement was detected.
- No protocol registration statement was detected.
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