Artikel ; Online: Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses.
2021 Band 20, Heft 3, Seite(n) 1591–1601
Abstract: A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic ... ...
| Abstract | A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next-generation sequencing (NGS) and mass spectrometry on nasopharyngeal swabs of COVID-19 patients to examine the clinical genome and proteome. Our study confirms the mutability of SARS-CoV-2 showing multiple single-nucleotide polymorphisms. NGS analysis detected 27 mutations, of which 14 are synonymous, 11 are missense, and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to a Bangladesh isolate and multiple origins of isolates within the country. Our proteomic analysis, for the first time, identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by high-resolution mass spectrometry, 8 matched to nucleocapsid protein, 2 to ORF9b, and 1 to spike glycoprotein and ORF3a, with remaining peptides mapping to ORF1ab polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 patients. Pathway analysis of these proteins points toward modulation in immune response, especially involving neutrophil and IL-12-mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutic approaches. |
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| Mesh-Begriff(e) | COVID-19/virology ; Coronavirus Nucleocapsid Proteins/genetics ; Genome, Viral ; Genomics ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions/genetics ; Host Microbial Interactions/physiology ; Humans ; Mutation ; Pandemics ; Phosphoproteins/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Polyproteins/genetics ; Proteome ; Proteomics ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/genetics ; Viral Proteins/genetics ; Viroporin Proteins/genetics |
| Chemische Substanzen | Coronavirus Nucleocapsid Proteins ; ORF1ab polyprotein, SARS-CoV-2 ; ORF3a protein, SARS-CoV-2 ; Phosphoproteins ; Polyproteins ; Proteome ; Spike Glycoprotein, Coronavirus ; Viral Proteins ; Viroporin Proteins ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2 |
| Sprache | Englisch |
| Erscheinungsdatum | 2021-02-08 |
| Erscheinungsland | United States |
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2078618-9 |
| ISSN | 1535-3907 ; 1535-3893 |
| ISSN (online) | 1535-3907 |
| ISSN | 1535-3893 |
| DOI | 10.1021/acs.jproteome.0c00808 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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