Functional evolution of SARS-COV-2 Spike protein: adaptation on translation and infection via surface charge of spike protein
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Abstract
The SARS-COV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-COV-2 sequence data from the end of 2019 to April 2022 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-COV-2 genes are undergoing negative purifying selection, while the spike protein gene (S-gene) is undergoing rapid positive selection. From the original strain to the alpha, delta and omicron variant types, the Ka/Ks of the S-gene increases, while the Ka/Ks within one variant type decreases over time. During the evolution, the codon usage did not evolve towards optimal translation and protein expression. In contrast, only S-gene mutations showed a remarkable trend on accumulating more positive charges. This facilitates the infection via binding human ACE2 for cell entry and binding furin for cleavage. Such a functional evolution emphasizes the survival strategy of SARS-COV-2, and indicated new druggable target to contain the viral infection. The nearly fully positively-charged interaction surfaces indicated that the infectivity of SARS-COV-2 virus may approach a limit.
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SciScore for 10.1101/2022.05.16.492062: (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
Experimental Models: Cell Lines Sentences Resources Sequencing data analysis: The original RNA-seq and Ribo-seq data (Calu3 cells infected with SARS-COV-2 for 7h) were downloaded form Gene Expression Omnibus database (GEO) under accession number GSE149973[9], In brief, all raw sequencing data low quality reads and linker were removed using fastp[10]. Calu3suggested: None2.2. Proteomic and RNC-seq expression data: Proteomic (quantitative technique: DIA, A549 cells infected with SARS-COV-2 for 24h) and RNC-seq (human HBE cell line) expression data were extracted from two independent studies supplementary materials, … SciScore for 10.1101/2022.05.16.492062: (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
Experimental Models: Cell Lines Sentences Resources Sequencing data analysis: The original RNA-seq and Ribo-seq data (Calu3 cells infected with SARS-COV-2 for 7h) were downloaded form Gene Expression Omnibus database (GEO) under accession number GSE149973[9], In brief, all raw sequencing data low quality reads and linker were removed using fastp[10]. Calu3suggested: None2.2. Proteomic and RNC-seq expression data: Proteomic (quantitative technique: DIA, A549 cells infected with SARS-COV-2 for 24h) and RNC-seq (human HBE cell line) expression data were extracted from two independent studies supplementary materials, respectively[13,14]. 2.3. A549suggested: NoneSoftware and Algorithms Sentences Resources Sequencing data analysis: The original RNA-seq and Ribo-seq data (Calu3 cells infected with SARS-COV-2 for 7h) were downloaded form Gene Expression Omnibus database (GEO) under accession number GSE149973[9], In brief, all raw sequencing data low quality reads and linker were removed using fastp[10]. Gene Expression Omnibussuggested: (Gene Expression Omnibus (GEO, RRID:SCR_005012)Lineage assignment using Pangolin lineage command line tool v3.0 (https://github.com/cov-lineages/pangolin) with standard model[15]. 2.4. Ka/Ks and charge evolution analysis: Due to high closely related (identity ∼ 99%) of SARS-COV-2 genomes, we used MAFFT v7 as multiple sequence aligner[16]. MAFFTsuggested: (MAFFT, RRID:SCR_011811)PyMol was used to calculate the surface electrostatic potential by Adaptive Poisson Boltzmann solver (APBS), the color scale range was set from −1.0 to 1.0 kT/Å. PyMolsuggested: (PyMOL, RRID:SCR_000305)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.
- 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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