Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples
Abhijith Biji,
Oyahida Khatun,
Shachee Swaraj,
Rohan Narayan,
Raju S. Rajmani,
Rahila Sardar,
Deepshikha Satish,
Simran Mehta,
Hima Bindhu,
Madhumol Jeevan,
Deepak K. Saini,
Amit Singh,
Dinesh Gupta,
Shashank Tripathi
Affiliations
Abhijith Biji
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Oyahida Khatun
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Shachee Swaraj
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Rohan Narayan
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Raju S. Rajmani
Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, India
Rahila Sardar
Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Deepshikha Satish
Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Simran Mehta
COVID-19 Diagnostic Facility, Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Hima Bindhu
COVID-19 Diagnostic Facility, Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Madhumol Jeevan
COVID-19 Diagnostic Facility, Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Deepak K. Saini
Molecular Reproduction & Developmental Genetics, Indian Institute of Science, Bengaluru, India
Amit Singh
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India
Dinesh Gupta
Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Shashank Tripathi
Microbiology & Cell Biology Department, Indian Institute of Science, Bengaluru, India; Centre for Infectious Disease Research, Indian Institute of Science, Bengaluru, India; Corresponding author: Dr. Shashank Tripathi, Indian Institute of Science, Microbiology and Cell Biology, Centre For Infectious Disease Research, C.V.Raman Avenue, Indian Institute of Science, Bengaluru, Karnataka 560012, India.
Background: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets. Methods: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model. Findings: The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs. Interpretation: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. Funding: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.
