While vaccine development for COVID-19 has progressed rapidly, the discovery of prognostic markers and antiviral drugs has been lagging behind. Several research groups have examined the host response in the respiratory tract to SARS-CoV-2 infection using OMICs technologies and large amounts of Big Data have been generated. Careful analysis of these data can provide insights required for COVID-19 prognosis and antiviral development.
A recent study, led by Shashank Tripathi from the Centre for Infectious Diseases Research and published in EbioMedicine, reports two novel findings: a specific gene signature in nasal swabs which can predict COVID-19 severity, and the potential offered by an FDA-approved drug (Auranofin) for COVID-19 therapy.
Current methods of assessing COVID-19 severity involve drawing blood or imaging the chest, both of which require a hospital visit. In the study, the researchers conducted a meta-analysis of COVID-19 OMICs data from nasopharyngeal samples, which revealed host factors that are consistently upregulated during infection. They were able to identify specific genes belonging to the S100 family (S100A6, S100A8, S100A9, and S100P) which could serve as prognostic markers of severe COVID-19. This gene signature can be detected by RT-PCR in the nasal swabs which are collected for COVID-19 diagnosis.
In the study, the researchers also identified multiple host processes which may be involved in virus replication and disease progression, and may serve as targets for host-directed therapy. Crucially, a redox regulatory protein called Thioredoxin (TXN) was found to be consistently upregulated in COVID-19 patients. Auranofin, an FDA-approved drug that targets the enzyme thioredoxin reductase and blocks the thioredoxin pathway, was found to mitigate SARS-CoV-2 replication in cell culture as well as in the preclinical Syrian hamster model. Auranofin is a safe and economical drug used for arthritis treatment. The study, therefore, suggests that it could serve as a promising COVID-19 antiviral.
The researchers plan to take these findings forward to clinical trials, with support from industry and clinical partners.
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, Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples, EBioMedicine, Volume 70, 2021, 103525, ISSN 2352-3964.