Transcription Factor Driven Gene Regulation in COVID-19 Patients

Viruses. 2023 May 18;15(5):1188. doi: 10.3390/v15051188.

Abstract

SARS-CoV-2 and its many variants have caused a worldwide emergency. Host cells colonised by SARS-CoV-2 present a significantly different gene expression landscape. As expected, this is particularly true for genes that directly interact with virus proteins. Thus, understanding the role that transcription factors can play in driving differential regulation in patients affected by COVID-19 is a focal point to unveil virus infection. In this regard, we have identified 19 transcription factors which are predicted to target human proteins interacting with Spike glycoprotein of SARS-CoV-2. Transcriptomics RNA-Seq data derived from 13 human organs are used to analyse expression correlation between identified transcription factors and related target genes in both COVID-19 patients and healthy individuals. This resulted in the identification of transcription factors showing the most relevant impact in terms of most evident differential correlation between COVID-19 patients and healthy individuals. This analysis has also identified five organs such as the blood, heart, lung, nasopharynx and respiratory tract in which a major effect of differential regulation mediated by transcription factors is observed. These organs are also known to be affected by COVID-19, thereby providing consistency to our analysis. Furthermore, 31 key human genes differentially regulated by the transcription factors in the five organs are identified and the corresponding KEGG pathways and GO enrichment are also reported. Finally, the drugs targeting those 31 genes are also put forth. This in silico study explores the effects of transcription factors on human genes interacting with Spike glycoprotein of SARS-CoV-2 and intends to provide new insights to inhibit the virus infection.

Keywords: COVID-19; RNA-Seq expression; SARS-CoV-2; drug repurposing; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / genetics
  • Gene Expression Regulation
  • Glycoproteins / genetics
  • Humans
  • SARS-CoV-2
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • Glycoproteins

Grants and funding

This work was carried out during the tenure of an ERCIM ‘Alain Bensoussan’ Fellowship Program awarded to Nimisha Ghosh. This work has also been partially supported by the CRG short-term research grant on COVID-19 (CVD/2020/000991) from the Science and Engineering Research Board (SERB), Department of Science and Technology, Govt. of India. This work is also funded by “BIOSYS2—Optimization, Models and Algorithms for Bioinformatics and System Biology” project (DIT.AD021.128) of the Institute for System Analysis and Computer Science “Antonio Ruberti”—National Research Council of Italy.