Epitranscriptomic changes during SARS-CoV-2 infection: Understanding post-COVID-19 syndrome and develop novel therapeutic strategy

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for coronavirus disease 2019 (COVID-19) pandemic, has affected millions of people around the globe with serious public-health emergency. Knowledge of host-viral interaction is essential to understand long term COVID-19 related symptoms.

Current proposal deals with epitranscriptomic (biochemical modifications in RNA) changes in host cell RNA transcripts during infection with SARS-CoV-2 leading to change in gene expression.

Our initial observation suggests drastic loss in host cell epitranscriptome in the SARS-COV-2 infected cells which coincides with change in cellular localization of the key enzyme involve in RNA modification.

We propose loss of host cell epitranscriptome drives long-term changes in the infected cells and contribute to long COVID-19 syndrome.

Blocking nuclear export protein XPO1 could reverse cellular localization of the epitranscriptomic writer enzyme and rescue epitranscriptomic signature of the infected host cells.

Finally using the AI ​​integrated pharmacophore-based method we plan to develop novel inhibitors with higher specificity and less toxicity against nuclear export protein XPO1 as an antiviral therapeutic approach against SARS-CoV-2.