Proteo-genomic analysis of SARS-CoV-2: A clinical landscape of SNPs, COVID-19 proteome and host responses

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of 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 clinical genome and proteome. Our study confirms the hyper mutability of SARS-CoV-2 showing multiple SNPs. 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 Bangladesh isolate and multiple origins of isolates within a 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 HRMS, 8 matched to nucleocapsid protein, 2 to ORF9b, 1 to spike glycoprotein and ORF3a, with remaining 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 towards 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 therapeutics. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Authors thank funding for the study by Department of Biotechnology and DBT-IISc Partnership grant. ST acknowledge fellowship from IISc. SK acknowledge fellowship from DBT-IISc Postdoctoral Research Associateship. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institute human ethics committee (IHEC). IHEC NO. 19-01092020 All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Mass spectrometry proteomics data acquired on nasopharyngeal swabs have been deposited to the ProteomeXchange Consortium via the PRIDE15 partner repository under dataset identifiers PXD021896 and 10.6019/PXD021896. The SARS-CoV-2 whole genome sequences have been submitted to NCBI under the accession number PRJNA668889. * SARS-CoV-2 : Severe acute respiratory syndrome coronavirus 2 COVID-19 : Coronavirus disease 2019 RT-PCR : Reverse transcription-polymerase chain reaction GISAID : Global Initiative on Sharing All Influenza Data HRMS : High-resolution mass spectrometry NGS : Next-generation sequencing SNPs : Single Nucleotide Polymorphism GO : Gene Ontology