Tiotropium is Predicted to be a Promising Drug for COVID-19 Through Transcriptome-Based Comprehensive Molecular Pathway Analysis

Viruses
Keunsoo KangYoonjung Choi

Abstract

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects almost everyone in the world in many ways. We previously predicted antivirals (atazanavir, remdesivir and lopinavir/ritonavir) and non-antiviral drugs (tiotropium and rapamycin) that may inhibit the replication complex of SARS-CoV-2 using our molecular transformer-drug target interaction (MT-DTI) deep-learning-based drug-target affinity prediction model. In this study, we dissected molecular pathways upregulated in SARS-CoV-2-infected normal human bronchial epithelial (NHBE) cells by analyzing an RNA-seq data set with various bioinformatics approaches, such as gene ontology, protein-protein interaction-based network and gene set enrichment analyses. The results indicated that the SARS-CoV-2 infection strongly activates TNF and NFκB-signaling pathways through significant upregulation of the TNF, IL1B, IL6, IL8, NFKB1, NFKB2 and RELB genes. In addition to these pathways, lung fibrosis, keratinization/cornification, rheumatoid arthritis, and negative regulation of interferon-gamma production pathways were also significantly upregulated. We observed that these pathologic features of SARS-CoV-2 are similar ...Continue Reading

References

Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Laszlo Lorand, Robert M Graham
Sep 4, 2003·Genome Research·Paul D ThomasApurva Narechania
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·Eleonora CandiGerry Melino
Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Oct 30, 2007·The Journal of Clinical Investigation·Jun ArayaStephen L Nishimura
Aug 30, 2008·Respiration; International Review of Thoracic Diseases·Ken IesatoHiroshi Shirasawa
Oct 7, 2008·The New England Journal of Medicine·Donald P TashkinUNKNOWN UPLIFT Study Investigators
Nov 21, 2009·Pharmacogenetics and Genomics·Augusto A LitonjuaRuss B Altman
Apr 7, 2010·Pulmonary Pharmacology & Therapeutics·L Wollin, M P Pieper
Sep 22, 2010·International Journal of Chronic Obstructive Pulmonary Disease·Kazuhito AsanoHiroaki Nakajima
Mar 1, 2011·Respiratory Research·Gabriela VaccaAdrian Gillissen
May 17, 2011·PloS One·Neil R HackettRonald G Crystal
Jun 28, 2011·American Journal of Respiratory and Critical Care Medicine·Keith C OlsenPatricia J Sime
Oct 18, 2011·International Journal of Chronic Obstructive Pulmonary Disease·Isao SuzakiHarumi Suzaki
Nov 29, 2011·Journal of Cellular and Molecular Medicine·Jing ZhangPeter N Black
Jan 10, 2012·Handbook of Experimental Pharmacology·Kalmia S Buels, Allison D Fryer
Mar 1, 2012·The European Respiratory Journal·Mutsuo YamayaRyoichi Nagatomi
Mar 7, 2012·Microbiology and Molecular Biology Reviews : MMBR·Jennifer R TisoncikMichael G Katze
Mar 28, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jill A FielhaberArnold S Kristof
Sep 4, 2012·The New England Journal of Medicine·Huib A M KerstjensEric D Bateman
Dec 12, 2012·Veterinary Immunology and Immunopathology·Mario Delgado-OrtegaFrançois Meurens
Jun 25, 2013·Biochimica Et Biophysica Acta·Leopold EckhartWim Declercq
Jan 15, 2014·Seminars in Immunology·Jeffrey J BabonNicos A Nicola
Jun 4, 2014·Biochimica Et Biophysica Acta·Mark D TurnerDaniel J Pennington
Aug 26, 2014·Nature Biotechnology·Davide RissoSandrine Dudoit
Nov 5, 2014·Tuberculosis and Respiratory Diseases·Ho-Kee Yum, I-Nae Park
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Mar 27, 2016·The Journal of Pharmacology and Experimental Therapeutics·Hannes BucherKlaus J Erb
Jun 10, 2016·Expert Opinion on Drug Safety·Huib A M Kerstjens, Paul M O'Byrne
Sep 30, 2016·The World Allergy Organization Journal·David M G Halpin
May 10, 2017·Multidisciplinary Respiratory Medicine·Dejan RadovanovicMarco Mantero
Aug 18, 2017·International Journal of Chronic Obstructive Pulmonary Disease·Dimitrios ToumpanakisTheodoros Vassilakopoulos
Sep 7, 2017·The New England Journal of Medicine·Yumin ZhouPixin Ran
Nov 22, 2017·Signal Transduction and Targeted Therapy·Ting LiuShao-Cong Sun
Feb 9, 2018·JCI Insight·Amal HoussainiSerge Adnot

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE147507
GM-CSF

Methods Mentioned

BETA
Profiler
RNA-seq

Software Mentioned

PANTHER
DESeq2
Morpheus
NetworkAnalyst
: Profiler
RUVSeq
FGSEA

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Related Papers

American Family Physician
Clarissa Kripke
The New England Journal of Medicine
Yoon K LokeCurt D Furberg
The New England Journal of Medicine
Katia M C VerhammeMiriam C J M Sturkenboom
The New England Journal of Medicine
Christine R Jenkins
The New England Journal of Medicine
Robert A Wise
© 2021 Meta ULC. All rights reserved