Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures

Abstract The outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug...

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Autores principales:	Lihong Peng, Ling Shen, Junlin Xu, Xiongfei Tian, Fuxing Liu, Juanjuan Wang, Geng Tian, Jialiang Yang, Liqian Zhou
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af5e44d92cc242c89e793045016603ee
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spelling	oai:doaj.org-article:af5e44d92cc242c89e793045016603ee2021-12-02T13:18:02ZPrioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures10.1038/s41598-021-83737-52045-2322https://doaj.org/article/af5e44d92cc242c89e793045016603ee2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83737-5https://doaj.org/toc/2045-2322Abstract The outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug Association (VDA) datasets. By incorporating VDAs with the similarity between drugs and that between viruses, we constructed a heterogeneous Virus-Drug network. A novel Random Walk with Restart method (VDA-RWR) was then developed to identify possible VDAs related to SARS-CoV-2. We compared VDA-RWR with three state-of-the-art association prediction models based on fivefold cross-validations (CVs) on viruses, drugs and virus-drug associations on three datasets. VDA-RWR obtained the best AUCs for the three fivefold CVs, significantly outperforming other methods. We found two small molecules coming together on the three datasets, that is, remdesivir and ribavirin. These two chemical agents have higher molecular binding energies of − 7.0 kcal/mol and − 6.59 kcal/mol with the domain bound structure of the human receptor angiotensin converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein, respectively. Interestingly, for the first time, experimental results suggested that navitoclax could be potentially applied to stop SARS-CoV-2 and remains to further validation.Lihong PengLing ShenJunlin XuXiongfei TianFuxing LiuJuanjuan WangGeng TianJialiang YangLiqian ZhouNature 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 Lihong Peng Ling Shen Junlin Xu Xiongfei Tian Fuxing Liu Juanjuan Wang Geng Tian Jialiang Yang Liqian Zhou Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
description	Abstract The outbreak of a novel febrile respiratory disease called COVID-19, caused by a newfound coronavirus SARS-CoV-2, has brought a worldwide attention. Prioritizing approved drugs is critical for quick clinical trials against COVID-19. In this study, we first manually curated three Virus-Drug Association (VDA) datasets. By incorporating VDAs with the similarity between drugs and that between viruses, we constructed a heterogeneous Virus-Drug network. A novel Random Walk with Restart method (VDA-RWR) was then developed to identify possible VDAs related to SARS-CoV-2. We compared VDA-RWR with three state-of-the-art association prediction models based on fivefold cross-validations (CVs) on viruses, drugs and virus-drug associations on three datasets. VDA-RWR obtained the best AUCs for the three fivefold CVs, significantly outperforming other methods. We found two small molecules coming together on the three datasets, that is, remdesivir and ribavirin. These two chemical agents have higher molecular binding energies of − 7.0 kcal/mol and − 6.59 kcal/mol with the domain bound structure of the human receptor angiotensin converting enzyme 2 (ACE2) and the SARS-CoV-2 spike protein, respectively. Interestingly, for the first time, experimental results suggested that navitoclax could be potentially applied to stop SARS-CoV-2 and remains to further validation.
format	article
author	Lihong Peng Ling Shen Junlin Xu Xiongfei Tian Fuxing Liu Juanjuan Wang Geng Tian Jialiang Yang Liqian Zhou
author_facet	Lihong Peng Ling Shen Junlin Xu Xiongfei Tian Fuxing Liu Juanjuan Wang Geng Tian Jialiang Yang Liqian Zhou
author_sort	Lihong Peng
title	Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
title_short	Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
title_full	Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
title_fullStr	Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
title_full_unstemmed	Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures
title_sort	prioritizing antiviral drugs against sars-cov-2 by integrating viral complete genome sequences and drug chemical structures
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af5e44d92cc242c89e793045016603ee
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Prioritizing antiviral drugs against SARS-CoV-2 by integrating viral complete genome sequences and drug chemical structures

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