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.

Introduction: In December 2019, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak occurred and caused the coronavirus disease of 2019 (COVID-19), which affected ~ 190 countries. The World Health Organization (WHO) has declared COVID-19 a pandemic on 11 th March 2020. Area covered: In the review, a comprehensive analysis of the recent developments of the COVID-19 pandemic has been provided, including the structural characterization of the virus, the current worldwide status of the disease, various detection strategies, drugs recommended for the effective treatment, and progress of vaccine development programs by different countries. This report was constructed by following a systematic literature search of bibliographic databases of published reports of relevance until 1 st September 2020. Expert opinion: Currently, the countries are opening businesses despite a spike in the number of COVID-19 cases. The pharmaceutical industries are developing clinical diagnostic kits, medicines, and vaccines. They target different approaches, including repurposing the already approved diagnosis and treatment options for similar CoVs. At present, over ~200 vaccine candidates are being developed against COVID-19. Future research may unravel the genetic variations or polymorphisms that dictate these differences in susceptibilities to the disease.

Coronavirus disease 2019 (COVID-19) pandemic has lasted more than a year since its first case in December 2019 and yet its social and economic burden continues to grow. While a tremendous amount of OMICs data has been generated from COVID-19 patient samples, the host antiviral response and markers of disease progression remain to be completely delineated. In this study, we have conducted a meta-analysis of published transcriptome and proteome profiles of the nasal swab and bronchioalveolar lavage fluid (BALF) samples of COVID-19 patients to identify high confidence upregulated host factors. This was followed by rank ordering, shortlisting, and validation of overexpression of a set of host factors in a nasal swab/BALF samples from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. This led to the identification of host antiviral response in the upper respiratory tract and potential prognostic markers. Notably, SEPRIN B3 and Thioredoxin were identified as potential antiviral factors. In addition, several S100 family proteins were found to be upregulated in COVID-19 specific and disease severity dependent manner. Overall, this study provides novel insights into the host antiviral mechanisms and COVID-19 disease progression.

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