Comprehensive mapping of metabolic perturbations in emerging and re-emerging RNA viruses for novel therapeutic approaches

Natural epidemics and outbreaks of emerging and re-emerging infectious diseases are growing global problems and primarily attributed to the RNA viruses like SARS-CoV-2, Crimean Congo Hemorrhagic fever viruses (CCHFV), dengue viruses (DENV) etc.

Viruses exploit the host metabolic machinery to meet their biosynthetic demands, making these host pathways potential therapeutic targets.

The present proposal is based on the hypothesis that RNA viruses exploit host metabolism to evade or delay host antiviral response by modulating the flux-balance of the central carbon metabolism (CCM) that can aid as antiviral strategies.

Using computer-guided approaches we aim to develop RNA virus-specific stoichiometric metabolic models and flux analysis to predict the metabolic perturbation that can inhibit the virus production using integrative transcriptomics, phospho-proteomics and metabolomics of the SARS-CoV-2, CCHFV and DENV infected and non-infected cells (aim#1).

We also use genome-scale metabolic models using transcriptomics data from cohorts from endemic regions for revealing the metabolic perturbation in RNA viruses (aim#2).

Finally we shall modulate CCM in vitro and ex vivo to achieve the metabolic inhibition of the viral reproduction to understand the mechanism of anti-viral defense (aim#2).

The study will also offer new possibilities for metabolic control of viral replication and reproduction and rationale for developing antivirals against emerging and re-emerging viruses.