Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

Biji, A and Khatun, O and Swaraj, S and Narayan, R and Rajmani, RS and Sardar, R and Satish, D and Mehta, S and Bindhu, H and Jeevan, M and Saini, DK and Singh, A and Gupta, D and Tripathi, S (2021) Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples. In: EBioMedicine, 70 .

Preview	PDF ebi_med_70_2021.pdf - Published Version Download (3MB) | Preview
	Archive (ZIP) ScienceDirect_files_17Sep2021_08-55-12.750.zip - Published Supplemental Material Download (10MB)

Abstract

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. © 2021 The Author(s)

Item Type:	Journal Article
Publication:	EBioMedicine
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to Authors
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	16 Nov 2021 11:03
Last Modified:	16 Nov 2021 11:03
URI:	http://eprints.iisc.ac.in/id/eprint/69828

Actions (login required)

View Item