Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics.

Scientific Reports
Hu ZhuRuili Huang

Abstract

The recent global pandemic of the Coronavirus disease 2019 (COVID-19) caused by the new coronavirus SARS-CoV-2 presents an urgent need for the development of new therapeutic candidates. Many efforts have been devoted to screening existing drug libraries with the hope to repurpose approved drugs as potential treatments for COVID-19. However, the antiviral mechanisms of action of the drugs found active in these phenotypic screens remain largely unknown. In an effort to deconvolute the viral targets in pursuit of more effective anti-COVID-19 drug development, we mined our in-house database of approved drug screens against 994 assays and compared their activity profiles with the drug activity profile in a cytopathic effect (CPE) assay of SARS-CoV-2. We found that the autophagy and AP-1 signaling pathway activity profiles are significantly correlated with the anti-SARS-CoV-2 activity profile. In addition, a class of neurology/psychiatry drugs was found to be significantly enriched with anti-SARS-CoV-2 activity. Taken together, these results provide new insights into SARS-CoV-2 infection and potential targets for COVID-19 therapeutics, which can be further validated by in vivo animal studies and human clinical trials.

References

Nov 19, 2003·Biochemical and Biophysical Research Communications·Runtao HeXuguang Li
Nov 20, 2004·Science·Gwendolyn F ElphickWalter J Atwood
Nov 27, 2004·Journal of Cell Science·Jochen HessMarina Schorpp-Kistner
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Menghang XiaMarshall Nirenberg
May 6, 2011·Environmental Health Perspectives·Ruili HuangChristopher P Austin
Feb 14, 2012·Journal of Cell Science·Yajuan GuoWei Liu
Mar 2, 2012·Nature Reviews. Drug Discovery·Jack W ScannellBrian Warrington
Dec 4, 2012·Viruses·Helena J Maier, Paul Britton
Jun 4, 2015·Emerging Microbes & Infections·Jennifer KouznetsovaAdolfo García-Sastre
Jun 8, 2015·Lancet·Alimuddin ZumlaStanley Perlman
Feb 13, 2016·Nature Reviews. Drug Discovery·Alimuddin ZumlaKwok-Yung Yuen
May 12, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yuan LiWen-Xing Ding
Dec 10, 2016·Chemical Research in Toxicology·Nicole C KleinstreuerRichard Judson
May 28, 2019·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Christian Bailly
Jun 22, 2019·Annual Review of Microbiology·To Sing Fung, Ding Xiang Liu
Oct 5, 2019·Drug Discovery Today·Ruili HuangChristopher P Austin
Mar 25, 2020·International Journal of Antimicrobial Agents·Philippe GautretDidier Raoult
Apr 1, 2020·International Journal of Biological Sciences·Naidi Yang, Han-Ming Shen
Apr 5, 2020·Pharmaceuticals·Martin D Bleasel, Gregory M Peterson
Apr 6, 2020·Travel Medicine and Infectious Disease·Yu-Chen CaoShi-Xue Dai
Apr 7, 2020·Antiviral Research·Leon CalyKylie M Wagstaff
Apr 10, 2020·The European Respiratory Journal·Sabrina BajwahIrene J Higginson
May 8, 2020·The New England Journal of Medicine·Joshua GelerisNeil W Schluger
May 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Furong ZengGuangtong Deng
May 20, 2020·L'Encéphale·Marion PlazeRaphaël Gaillard
May 24, 2020·The New England Journal of Medicine·John H BeigelUNKNOWN ACTT-1 Study Group Members
May 31, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shuofeng YuanKwok-Yung Yuen
Jun 6, 2020·Journal of Cell Science·Åsa B Birgisdottir, Terje Johansen
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Kirill GorshkovWei Zheng
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Laura RivaSumit K Chanda
Jun 9, 2020·BioRxiv : the Preprint Server for Biology·Kyle R BrimacombeMin Shen
Jun 12, 2020·Autophagy·Srinivasa Reddy BonamDaniel J Klionsky

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Related Papers

The Journal of Pharmacology and Experimental Therapeutics
Zeenat A ShyrWei Zheng
Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents
P Chellapandi, S Saranya
© 2021 Meta ULC. All rights reserved