tetano
Editor, Senior Moderator
J Proteome Res
. 2021 Feb 8.
doi: 10.1021/acs.jproteome.0c00808. Online ahead of print.
Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses
Sheetal Tushir[SUP] 1 [/SUP], Sathisha Kamanna[SUP] 1 [/SUP], Sujith S Nath[SUP] 1 [/SUP], Aishwarya Bhat[SUP] 1 [/SUP], Steffimol Rose[SUP] 1 [/SUP], Advait R Aithal[SUP] 1 [/SUP], Utpal Tatu[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; COVID-19 proteomics; SARS-CoV-2; genomics; host proteome; mass spectrometry; next-generation sequencing.
. 2021 Feb 8.
doi: 10.1021/acs.jproteome.0c00808. Online ahead of print.
Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses
Sheetal Tushir[SUP] 1 [/SUP], Sathisha Kamanna[SUP] 1 [/SUP], Sujith S Nath[SUP] 1 [/SUP], Aishwarya Bhat[SUP] 1 [/SUP], Steffimol Rose[SUP] 1 [/SUP], Advait R Aithal[SUP] 1 [/SUP], Utpal Tatu[SUP] 1 [/SUP]
Affiliations
- PMID: 33555895
- DOI: 10.1021/acs.jproteome.0c00808
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.
Keywords: COVID-19; COVID-19 proteomics; SARS-CoV-2; genomics; host proteome; mass spectrometry; next-generation sequencing.