Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

Commun Biol. 2021 May 17;4(1):590. doi: 10.1038/s42003-021-02095-0.


The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host-pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

MeSH terms

  • Binding Sites
  • COVID-19 / genetics*
  • COVID-19 / virology
  • Computational Biology / methods*
  • Cytokines / genetics
  • Databases, Genetic
  • Gene Expression Regulation
  • Genome, Viral
  • Host-Pathogen Interactions / genetics*
  • Humans
  • Pandemics*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Seq
  • SARS-CoV-2 / genetics*
  • Serpins / genetics
  • Signal Transduction / genetics
  • Transcriptome
  • Virus Replication / genetics


  • Cytokines
  • RNA, Viral
  • RNA-Binding Proteins
  • SERPINA3 protein, human
  • Serpins