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

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.