TY - JOUR
T1 - Transcriptome network analyses in human coronavirus infections suggest a rational use of immunomodulatory drugs for COVID-19 therapy
AU - Wong, Henry Sung Ching
AU - Guo, Chin Lin
AU - Lin, Gan Hong
AU - Lee, Kang Yun
AU - Okada, Yukinori
AU - Chang, Wei Chiao
N1 - Funding Information:
This work was supported by grants from Ministry of Science and Technology, Taiwan ( MOST109-2314-B-038-131 and MOST109-2628-B-038-012 ), and Taipei Medical University, Taiwan ( 12310-106079 ; Yusuke Nakamura Chair Professorship).
Publisher Copyright:
© 2021 Elsevier Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - COVID-19
KW - Drug repositioning
KW - SARS-CoV-2
KW - Transcriptomic and network analysis
UR - http://www.scopus.com/inward/record.url?scp=85099987378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099987378&partnerID=8YFLogxK
U2 - 10.1016/j.ygeno.2020.12.041
DO - 10.1016/j.ygeno.2020.12.041
M3 - Article
C2 - 33482326
AN - SCOPUS:85099987378
SN - 0888-7543
VL - 113
SP - 564
EP - 575
JO - Genomics
JF - Genomics
IS - 2
ER -