Elsevier

Genomics

Volume 113, Issue 2, March 2021, Pages 564-575
Genomics

Original Article
Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy

https://doi.org/10.1016/j.ygeno.2020.12.041Get rights and content
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Highlights

  • Rationalization of useful therapeutic targets against the COVID-19 is of urgent need.

  • Transcriptomic perturbation profiles of SARS-CoV ΔORF6 mutant revealing 55 genes and 238 ligands to reposition to COVID-19.

  • Immune checkpoint inhibitors targeting PD-L1 shows potential for COVID-19 treatment.

  • 16 Anatomical Therapeutic Chemical classes were valuable for further investigation to treat COVID-19.

Abstract

The recent outbreak of coronavirus disease 2019 (COVID-19) by SARS-CoV-2 has led to uptodate 24.3 M cases and 0.8 M deaths. It is thus in urgent need to rationalize potential therapeutic targets against the progression of diseases. An effective, feasible way is to use the pre-existing ΔORF6 mutant of SARS-CoV as a surrogate for SARS-CoV-2, since both lack the moiety responsible for interferon antagonistic effects. By analyzing temporal profiles of upregulated genes in ΔORF6-infected Calu-3 cells, we prioritized 55 genes and 238 ligands to reposition currently available medications for COVID-19 therapy. Eight of them are already in clinical trials, including dexamethasone, ritonavir, baricitinib, tofacitinib, naproxen, budesonide, ciclesonide and formoterol. We also pinpointed 16 drug groups from the Anatomical Therapeutic Chemical classification system, with the potential to mitigate symptoms of SARS-CoV-2 infection and thus to be repositioned for COVID-19 therapy.

Keywords

SARS-CoV-2
COVID-19
Transcriptomic and network analysis
Drug repositioning

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