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MicrobiologybioRxiv

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

A. Biji, O. Khatun, S. Swaraj, R. Narayan, R. Rajmani, R. Sardar, D. Satish, S. Mehta, H. Bindhu, M. Jeevan, D. K. Saini, A. Singh, D. Gupta, S. Tripathi

Abstract

While our battle with the COVID-19 pandemic continues, a multitude of Omics data has been generated from patient samples in various studies, which remains to be translated. We conducted a meta-analysis of published transcriptome and proteome profiles of nasal swab and bronchioalveolar lavage fluid (BALF) samples of COVID-19 patients, to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swab/BALF samples from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Analysis of these data revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of COVID-19 disease. Furthermore, Thioredoxin gene (TXN) was identified as a significant upregulated host factor in our overlap analysis. An FDA-approved drug Auranofin, which inhibits Thioredoxin reduction, was found to mitigate SARS-CoV-2 replication in vitro and in vivo in the hamster challenge model. Overall, this study translates COVID-19 host response Big Data into potential clinical interventions.

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