Viruses exploit the host metabolic machinery to meet their biosynthetic demands, making these host pathways potential therapeutic targets. We are interested in understanding how SARS-CoV-2 rewire host cell metabolism to facilitate optimal viral replication that can be a potential target for therapy. We combine unbiased integrated multi-omics technologies (transcriptomics, proteomics and metabolomics), with hypothesis-driven approaches (based on in vitro cell culture data). We amalgamate molecular biology, biochemistry, and structural biology with advanced cell culture systems and analysis of patient material to understand the host antiviral defense as well as its association with disease severity.
Historically, viral polymerases have been proven to be attractive targets for broad antiviral therapy.We also work to develop broad-spectrum antiviral targeting nsp12 (RNA dependent RNA polymerase; RdRp). Using computational and bioinformatics tools, we identified a group of small molecules that could potentially target SARS-CoV-2, which we are now performing in vitro assays.
The study will provide new possibilities for therapeutic modulation of immune responses through metabolic reprogramming, and rationale for the development of antivirals, against SARS-CoV-2. Our approach can, therefore also be utilized for drug repurposing targeting other RNA virus RdRp and will also create a knowledge bank for future pandemics.
1.Neogi U, Hill KJ, Ambikan AT, Heng X, Quinn TP, Byrareddy SN, Sönnerborg A, SarafianosSG, Singh K (2020) Feasibility of known RNA polymerase inhibitors as anti-SARS-CoV-2 drugs. (under communication)