Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) showed promising clinical efficacy toward COVID-19 (Coronavirus disease 2019) patients as potent painkillers and anti-inflammatory agents. However, the prospective anti-COVID-19 mechanisms of NSAIDs are not evidently exposed. Therefore, we inte...

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Autores principales:	Ki Kwang Oh, Md. Adnan, Dong Ha Cho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1047c48599614c479ea27965ba780431
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spelling	oai:doaj.org-article:1047c48599614c479ea27965ba7804312021-12-02T14:29:04ZNetwork pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-1910.1038/s41598-021-88313-52045-2322https://doaj.org/article/1047c48599614c479ea27965ba7804312021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88313-5https://doaj.org/toc/2045-2322Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) showed promising clinical efficacy toward COVID-19 (Coronavirus disease 2019) patients as potent painkillers and anti-inflammatory agents. However, the prospective anti-COVID-19 mechanisms of NSAIDs are not evidently exposed. Therefore, we intended to decipher the most influential NSAIDs candidate(s) and its novel mechanism(s) against COVID-19 by network pharmacology. FDA (U.S. Food & Drug Administration) approved NSAIDs (19 active drugs and one prodrug) were used for this study. Target proteins related to selected NSAIDs and COVID-19 related target proteins were identified by the Similarity Ensemble Approach, Swiss Target Prediction, and PubChem databases, respectively. Venn diagram identified overlapping target proteins between NSAIDs and COVID-19 related target proteins. The interactive networking between NSAIDs and overlapping target proteins was analyzed by STRING. RStudio plotted the bubble chart of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of overlapping target proteins. Finally, the binding affinity of NSAIDs against target proteins was determined through molecular docking test (MDT). Geneset enrichment analysis exhibited 26 signaling pathways against COVID-19. Inhibition of proinflammatory stimuli of tissues and/or cells by inactivating the RAS signaling pathway was identified as the key anti-COVID-19 mechanism of NSAIDs. Besides, MAPK8, MAPK10, and BAD target proteins were explored as the associated target proteins of the RAS. Among twenty NSAIDs, 6MNA, Rofecoxib, and Indomethacin revealed promising binding affinity with the highest docking score against three identified target proteins, respectively. Overall, our proposed three NSAIDs (6MNA, Rofecoxib, and Indomethacin) might block the RAS by inactivating its associated target proteins, thus may alleviate excessive inflammation induced by SARS-CoV-2.Ki Kwang OhMd. AdnanDong Ha ChoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ki Kwang Oh Md. Adnan Dong Ha Cho Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
description	Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) showed promising clinical efficacy toward COVID-19 (Coronavirus disease 2019) patients as potent painkillers and anti-inflammatory agents. However, the prospective anti-COVID-19 mechanisms of NSAIDs are not evidently exposed. Therefore, we intended to decipher the most influential NSAIDs candidate(s) and its novel mechanism(s) against COVID-19 by network pharmacology. FDA (U.S. Food & Drug Administration) approved NSAIDs (19 active drugs and one prodrug) were used for this study. Target proteins related to selected NSAIDs and COVID-19 related target proteins were identified by the Similarity Ensemble Approach, Swiss Target Prediction, and PubChem databases, respectively. Venn diagram identified overlapping target proteins between NSAIDs and COVID-19 related target proteins. The interactive networking between NSAIDs and overlapping target proteins was analyzed by STRING. RStudio plotted the bubble chart of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis of overlapping target proteins. Finally, the binding affinity of NSAIDs against target proteins was determined through molecular docking test (MDT). Geneset enrichment analysis exhibited 26 signaling pathways against COVID-19. Inhibition of proinflammatory stimuli of tissues and/or cells by inactivating the RAS signaling pathway was identified as the key anti-COVID-19 mechanism of NSAIDs. Besides, MAPK8, MAPK10, and BAD target proteins were explored as the associated target proteins of the RAS. Among twenty NSAIDs, 6MNA, Rofecoxib, and Indomethacin revealed promising binding affinity with the highest docking score against three identified target proteins, respectively. Overall, our proposed three NSAIDs (6MNA, Rofecoxib, and Indomethacin) might block the RAS by inactivating its associated target proteins, thus may alleviate excessive inflammation induced by SARS-CoV-2.
format	article
author	Ki Kwang Oh Md. Adnan Dong Ha Cho
author_facet	Ki Kwang Oh Md. Adnan Dong Ha Cho
author_sort	Ki Kwang Oh
title	Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
title_short	Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
title_full	Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
title_fullStr	Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
title_full_unstemmed	Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19
title_sort	network pharmacology approach to decipher signaling pathways associated with target proteins of nsaids against covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1047c48599614c479ea27965ba780431
work_keys_str_mv	AT kikwangoh networkpharmacologyapproachtodeciphersignalingpathwaysassociatedwithtargetproteinsofnsaidsagainstcovid19 AT mdadnan networkpharmacologyapproachtodeciphersignalingpathwaysassociatedwithtargetproteinsofnsaidsagainstcovid19 AT donghacho networkpharmacologyapproachtodeciphersignalingpathwaysassociatedwithtargetproteinsofnsaidsagainstcovid19
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Network pharmacology approach to decipher signaling pathways associated with target proteins of NSAIDs against COVID-19

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