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.
An experiment was conducted at Regional Agricultural Research Station, Kumarakom during 2014-15 with an objective to understand the genetic relationship of some superior Garcinia accessions having different geographic origin and maintained at germplasm collections of Regional Agricultural Research Station, Kumarakom, Kerala, India. Germplasm identification and characterization is an important link between conservation and utilization of plant genetic resources. In this study, random amplified polymorphic DNA (RAPD) markers were used to find out the genetic relationship of 30 garcinia accessions. This included two Garcinia varieties Amrutham and Haritham which were released during 2015 from this station. The primer OPM16 gave maximum number of polymorphic bands and OPAB16 produced least. Out of the total 397 alleles scored, 68.76 per cent were found to be polymorphic. The polymorphic information content (PIC) ranged between 0.14 (OPC 7) and 0.49 (OPAB 16) and marker index (MI) ranged from 0.01 (OPC 7) to 0.15 (OPM 16 and OPAB 16) among the primers used. Jaccard's similarity co-efficient between genotypes ranged from 0.462 to 0.991. An UPGMA dendrogram was constructed using NTSYS pc 2.02e software and showed two major clusters. The variety Amrutham did not form any cluster and stood alone in the group whereas Haritham clustered in the second group. This is the first report for the molecular based genetic diversity studies for these accessions.
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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