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

Henry Sung-Ching Wong; Chin-Lin Guo; Gan-Hong Lin; Kang-Yun Lee; Yukinori Okada; Wei-Chiao Chang

doi:10.1016/j.ygeno.2020.12.041

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

Genomics. 2021 Mar;113(2):564-575. doi: 10.1016/j.ygeno.2020.12.041. Epub 2021 Jan 20.

Authors

Henry Sung-Ching Wong¹, Chin-Lin Guo², Gan-Hong Lin³, Kang-Yun Lee⁴, Yukinori Okada⁵, Wei-Chiao Chang⁶

Affiliations

¹ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
² Institute of Physics, Academia Sinica, Taipei, Taiwan.
³ Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
⁴ Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
⁵ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan; Laboratory of Statistical Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
⁶ Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan; Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. Electronic address: wcc@tmu.edu.tw.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19 / immunology
COVID-19 Drug Treatment*
Cell Line
Gene Expression Profiling*
Humans
Immunologic Factors / pharmacology*
SARS-CoV-2 / immunology*
Transcriptome / drug effects*
Transcriptome / immunology

Substances

Immunologic Factors