Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 3, Pages 1591-1601Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.0c00808
Keywords
COVID-19; SARS-CoV-2; next-generation sequencing; mass spectrometry; COVID-19 proteomics; genomics; host proteome
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Funding
- DBT-IISc partnership grant
- ICMR project [93/01/2020-TImmIP/BMS]
- IISc
- DBT-IISc Postdoctoral Research Associateship
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The study utilized proteo-genomic and phylogenetic analyses to investigate the mutation patterns of SARS-CoV-2 and identified key host proteins that may modulate immune responses in COVID-19 patients. The findings provide insights into the host-virus interaction and potential avenues for developing diagnostic markers and therapeutic approaches.
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-CoV2 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 IL12-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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