Investigating the genomic landscape of novel coronavirus (2019-nCoV) to identify non-synonymous mutations for use in diagnosis and drug design
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Abstract
Novel coronavirus has wrecked medical and health care facilities claiming ~5% death tolls globally. All efforts to contain the pathogenesis either using inhibitory drugs or vaccines largely remained futile due to a lack of better understanding of the genomic feature of this virus. In the present study, we compared the 2019-nCoV with other coronaviruses, which indicated that bat-SARS like coronavirus could be a probable ancestor of the novel coronavirus. The protein sequence similarity of pangolin-hCoV and bat-hCoV with human coronavirus was higher as compared to their nucleotide similarity denoting the occurrence of more synonymous mutations in the genome. Phylogenetic and alignment analysis of 591 novel coronaviruses of different clades from Group I to Group V revealed several mutations and concomitant amino acid changes. Detailed investigation on nucleotide substitution unfolded 100 substitutions in the coding region of which 43 were synonymous and 57 were of non-synonymous type. The non-synonymous substitutions resulting into 57 amino acid changes were found to be distributed over different hCoV proteins with maximum on spike protein. An important diamino acid change RG to KR was observed in ORF9 protein. Additionally, several interesting features of the novel coronavirus genome have been highlighted in respect to various other human infecting viruses which may explain extreme pathogenicity, infectivity and simultaneously the reason behind failure of the antiviral therapies.
Summary
This study presents a comprehensive phylogenetic analysis of SARS-CoV2 isolates to understand discrete mutations that are occurring between patient samples. This analysis will provide an explanation for varying treatment efficacies of different inhibitory drugs and a future direction towards a combinatorial treatment therapies based on the kind of mutation in the viral genome.
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SciScore for 10.1101/2020.04.16.043273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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 …
SciScore for 10.1101/2020.04.16.043273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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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SciScore for 10.1101/2020.04.16.043273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Phylogenetic analyses of human novel coronavirus We investigated the phylogenetic analysis of 591 genomic sequences of hCoV obtained from GISAID database using RAxML methods . RAxMLsuggested: (RAxML, SCR_006086)The genomic sequences were aligned using MUSCLE program (v3.8.31) (Edgar, 2004). MUSCLEsuggested: (MUSCLE, SCR_011812)The alignment and tree … SciScore for 10.1101/2020.04.16.043273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Phylogenetic analyses of human novel coronavirus We investigated the phylogenetic analysis of 591 genomic sequences of hCoV obtained from GISAID database using RAxML methods . RAxMLsuggested: (RAxML, SCR_006086)The genomic sequences were aligned using MUSCLE program (v3.8.31) (Edgar, 2004). MUSCLEsuggested: (MUSCLE, SCR_011812)The alignment and tree were visualized using Jalview 2.11.0 (Waterhouse et al., 2009) and iTOL respectively (Letunic and Peer, 2007). Jalviewsuggested: (Jalview, SCR_006459)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).
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