Theme 4: Covid-19 research

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.

Graphic illustration of figure: Proposed binding of remdesivir-TP and mechanism of resistance to remdesivir (Neogi et al 2010, Pathogen)

Viruses exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Using several machine learning approaches after integrating the multi-omics data, 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 aim to combine unbiased multi-omics technologies (transcriptomics, proteomics and metabolomics) with hypothesis-driven approaches (based on our in vitro data). We have established a consortium of interdisciplinary experts to amalgamate molecular biology, biochemistry, structural biology and systems biology with advanced cell culture system and analysis of patient material, to understand the antiviral defense, i.e. how the cells fight with the invading viruses. We infected different cell lines with the virus and identified some essential components of a signaling pathway that the viruses potentially use. We believe modulating that signaling could lead to a new therapy for severely ill patients. 

We are also interested in developing broad spectrum antivirals targeting RNA-dependent RNA polymerase (RdRp) of RNA viruses including SARS-CoV-2. Historically, RdRp have been proven to be attractive targets for broad antiviral therapy. 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. It will also provide new possibilities for therapeutic modulation of immune responses, development of antivirals and vaccines.

Publications

Appelberg S, Gupta S, Ambikan AT, Mikaeloff F, Végvári Á, Akusjärvi SS, Benfeitas R, Sperk M, Ståhlberg M, Krishnan S et al: Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells. bioRxiv 2020:2020.2004.2030.070383.

Feasibility of Known RNA Polymerase Inhibitors as Anti-SARS-CoV-2 Drugs.
Neogi U, Hill KJ, Ambikan AT, Heng X, Quinn TP, Byrareddy SN, et al
Pathogens 2020 Apr;9(5):