Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 proteome and host responses

Tushir, Sheetal; Kamanna, Sathisha; Nath, Sujith S; Bhat, Aishwarya; Rose, Steffimol; Aithal, Advait R; Tatu, Utpal

doi:10.1101/2020.11.27.20237032

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…An average of ⩾11 mutations per sample with the insurgence of single-nucleotide substitutions was reported for SARS-CoV-2 [8, 49]. These mutations are categorised as amino acid changing SNP (single-nucleotide polymorphism), amino acid changing triplet, 5′ UTR-SNP and silent SNP.…”

Section: Genome Organisation Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Majumdar¹,

Niyogi²

2021

Epidemiol. Infect.

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The outbreak of pneumonia-like respiratory disorder at China and its rapid transmission world-wide resulted in public health emergency, which brought lineage B betacoronaviridae SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) into spotlight. The fairly high mutation rate, frequent recombination and interspecies transmission in betacoronaviridae are largely responsible for their temporal changes in infectivity and virulence. Investigation of global SARS-CoV-2 genotypes revealed considerable mutations in structural, non-structural, accessory proteins as well as untranslated regions. Among the various types of mutations, single-nucleotide substitutions are the predominant ones. In addition, insertion, deletion and frame-shift mutations are also reported, albeit at a lower frequency. Among the structural proteins, spike glycoprotein and nucleocapsid phosphoprotein accumulated a larger number of mutations whereas envelope and membrane proteins are mostly conserved. Spike protein and RNA-dependent RNA polymerase variants, D614G and P323L in combination became dominant world-wide. Divergent genetic variants created serious challenge towards the development of therapeutics and vaccines. This review will consolidate mutations in different SARS-CoV-2 proteins and their implications on viral fitness.

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Section: Genome Organisation Of Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Majumdar¹,

Niyogi²

2021

Epidemiol. Infect.

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“…Protein bands stained with Coomassie Brilliant Blue were excised precisely from SDS polyacrylamide gels and subjected to trypsin digestion and mass spectrometry, raw data analysis and processing using MaxQuant software (v1.6.2.10) and MS Excel essentially as described elsewhere (Tushir et al, 2021), but against the Mus musculus proteome.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Minus one frameshifted puromycin N-acetyltransferase is targeted to the nucleolus: sporadic but reproducible chimera formation by a transfected Lc3b construct

Thekkinghat

Rangarajan

2022

Preprint

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Map1Lc3b is a protein that has pivotal functions in cellular autophagy. At least three groups in the past decade have reported its presence in the nucleoli of cells, but its functions in that organelle remain unknown. We isolated a few clonal populations of cells stably expressing V5-tagged mouse Lc3b highly enriched in the nucleoli, but the frequency of occurrence of such clones was strikingly low. The phenomenon was readily reproducible, though the protein in the nucleolus puzzlingly had varying molecular masses in different clones but consistently displayed a very strong interaction with the mitochondrial protein C1qbp, which has well-documented functions in the nucleolus. We investigated further and discovered that, in at least one of the clones, Lc3b had formed a chimera with the puromycin resistance gene in the plasmid, plausibly by illegitimate recombination during or after integration of the construct into the cellular genomic DNA. The -1 shifted reading frame of puromycin N-acetyltransferase (pac) can encode a protein that is equally long as the one encoded by the complete pac ORF, but is targeted to the nucleoli due to a drastic shift in the isoelectric point (pI). Notably, this set of events again brings into focus the low threshold often reported for recombination events to occur in eukaryotic cells, the multiple factors influencing them, and calls for increased vigilance in experiments involving DNA transfection and gene targeting.

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Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 proteome and host responses

Cited by 3 publications

References 34 publications

SARS-CoV-2 mutations: the biological trackway towards viral fitness

SARS-CoV-2 mutations: the biological trackway towards viral fitness

Minus one frameshifted puromycin N-acetyltransferase is targeted to the nucleolus: sporadic but reproducible chimera formation by a transfected Lc3b construct

Microarrays and NGS for Drug Discovery

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