Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses

Tushir, S and Kamanna, S and Nath, SS and Bhat, A and Rose, S and Aithal, AR and Tatu, U (2021) Proteo-Genomic Analysis of SARS-CoV-2: A Clinical Landscape of Single-Nucleotide Polymorphisms, COVID-19 Proteome, and Host Responses. In: Journal of Proteome Research .

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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. ©

Item Type:	Journal Article
Publication:	Journal of Proteome Research
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	19 Mar 2021 09:32
Last Modified:	19 Mar 2021 09:32
URI:	http://eprints.iisc.ac.in/id/eprint/68401

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