Mutational spectra of SARS‐CoV‐2 orf1ab polyprotein and signature mutations in the United States of America
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Abstract
The pandemic COVID‐19 outbreak has been caused due to SARS‐CoV‐2 pathogen, resulting in millions of infections and deaths worldwide, the United States being on top at the present moment. The long, complex orf1ab polyproteins of SARS‐CoV‐2 play an important role in viral RNA synthesis. To assess the impact of mutations in this important domain, we analyzed 1134 complete protein sequences of the orf1ab polyprotein from the NCBI virus database from affected patients across various states of the United States from December 2019 to 25 April 2020. Multiple sequence alignment using Clustal Omega followed by statistical significance was calculated. Four significant mutations T265I (nsp 2), P4715L (nsp 12), and P5828L and Y5865C (both at nsp 13) were identified in important nonstructural proteins, which function either as replicase or helicase. A comparative analysis shows 265 T→I, 5828 P→L, and 5865Y→C are unique to the United States and not reported from Europe or Asia; while one, 4715 P→L is predominant in both Europe and the United States. Mutational changes in amino acids are predicted to alter the structure and function of the corresponding proteins, thereby, it is imperative to consider the mutational spectra while designing new antiviral therapeutics targeting viral orf1ab.
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SciScore for 10.1101/2020.05.01.071654: (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 ORF1ab protein sequence retrieval from the database: The protein sequences were retrieved from “NCBI Virus” database, specific input was “SARS-CoV-2”. Virus”suggested: NoneMultiple Sequence Alignment (MSA) and analysis of mutational spectra: Clustal Omega (5) was employed to align multiple sequences of each of the above-mentioned groups. Clustal Omegasuggested: (Clustal Omega, RRID:SCR_001591)Homology Modelling and simulation of protein structure: Structures of the associated non structural proteins for wild type were reported at I-Tasser server, however, the structures were not available … SciScore for 10.1101/2020.05.01.071654: (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 ORF1ab protein sequence retrieval from the database: The protein sequences were retrieved from “NCBI Virus” database, specific input was “SARS-CoV-2”. Virus”suggested: NoneMultiple Sequence Alignment (MSA) and analysis of mutational spectra: Clustal Omega (5) was employed to align multiple sequences of each of the above-mentioned groups. Clustal Omegasuggested: (Clustal Omega, RRID:SCR_001591)Homology Modelling and simulation of protein structure: Structures of the associated non structural proteins for wild type were reported at I-Tasser server, however, the structures were not available for the varied amino acid alteration. I-Tassersuggested: (I-TASSER, RRID:SCR_014627)To identify the alteration, Homology Modelling method by I-Tasser was used to generate secondary structure, which was then superimposed with the wild type using UCSF Chimera and PyMOL for easy visualization and comparison. 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.
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