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

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 d...

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Autores principales:	Hu Zhu, Catherine Z. Chen, Srilatha Sakamuru, Jinghua Zhao, Deborah K. Ngan, Anton Simeonov, Mathew D. Hall, Menghang Xia, Wei Zheng, Ruili Huang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a6ca3565e3544ed8363995ed6f8f3f9
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spelling	oai:doaj.org-article:1a6ca3565e3544ed8363995ed6f8f3f92021-12-02T14:02:54ZMining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics10.1038/s41598-021-86110-82045-2322https://doaj.org/article/1a6ca3565e3544ed8363995ed6f8f3f92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86110-8https://doaj.org/toc/2045-2322Abstract 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.Hu ZhuCatherine Z. ChenSrilatha SakamuruJinghua ZhaoDeborah K. NganAnton SimeonovMathew D. HallMenghang XiaWei ZhengRuili HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hu Zhu Catherine Z. Chen Srilatha Sakamuru Jinghua Zhao Deborah K. Ngan Anton Simeonov Mathew D. Hall Menghang Xia Wei Zheng Ruili Huang Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
description	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.
format	article
author	Hu Zhu Catherine Z. Chen Srilatha Sakamuru Jinghua Zhao Deborah K. Ngan Anton Simeonov Mathew D. Hall Menghang Xia Wei Zheng Ruili Huang
author_facet	Hu Zhu Catherine Z. Chen Srilatha Sakamuru Jinghua Zhao Deborah K. Ngan Anton Simeonov Mathew D. Hall Menghang Xia Wei Zheng Ruili Huang
author_sort	Hu Zhu
title	Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
title_short	Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
title_full	Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
title_fullStr	Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
title_full_unstemmed	Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics
title_sort	mining of high throughput screening database reveals ap-1 and autophagy pathways as potential targets for covid-19 therapeutics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1a6ca3565e3544ed8363995ed6f8f3f9
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Mining of high throughput screening database reveals AP-1 and autophagy pathways as potential targets for COVID-19 therapeutics

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