Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection

TL;DR

This study compares transcriptomic data from various coronavirus infections to identify key epigenetic targets, suggesting epigenetic machinery as a potential therapeutic avenue for COVID-19.

Contribution

It provides a comprehensive analysis of epigenetic regulation in SARS-CoV-2 infection, identifying novel candidate proteins involved in the host response.

Findings

Identified key epigenetic regulators like EP300, MOV10, RELA, TRIM25

Discovered over 60 proteins with therapeutic potential

Highlighted epigenetic machinery as a treatment target

Abstract

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2. In this study, we analyzed multiple transcriptomes obtained from cell lines infected with MERS-CoV, SARS-CoV and SARS-CoV-2, and from COVID-19 patient-derived samples. Using integrative analyses of gene co-expression networks and de-novo pathway enrichment, we characterize different gene modules and protein pathways enriched with Transcription Factors or Epifactors relevant for SARS-CoV-2 infection. We identified EP300, MOV10, RELA and TRIM25 as top candidates, and more than 60 additional proteins involved in the epigenetic response during viral infection that have therapeutic potential. Our results show that targeting the epigenetic machinery could be a feasible alternative to treat COVID-19.