Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis

Abstract Understanding the molecular basis of fibrosis, the lethal complication of COVID-19, is urgent. By the analysis of RNA-sequencing data of SARS-CoV-2-infected cells combined with data mining we identified genes involved in COVID-19 progression. To characterize their implication in the fibrosi...

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Autores principales:	Elmira R. Vagapova, Timofey D. Lebedev, Vladimir S. Prassolov
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af657faedb774b16b9c79f1776b9032d
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spelling	oai:doaj.org-article:af657faedb774b16b9c79f1776b9032d2021-12-02T14:49:24ZViral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis10.1038/s41598-021-90701-w2045-2322https://doaj.org/article/af657faedb774b16b9c79f1776b9032d2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90701-whttps://doaj.org/toc/2045-2322Abstract Understanding the molecular basis of fibrosis, the lethal complication of COVID-19, is urgent. By the analysis of RNA-sequencing data of SARS-CoV-2-infected cells combined with data mining we identified genes involved in COVID-19 progression. To characterize their implication in the fibrosis development we established a correlation matrix based on the transcriptomic data of patients with idiopathic pulmonary fibrosis. With this method, we have identified a cluster of genes responsible for SARS-CoV-2-fibrosis including its entry receptor ACE2 and epidermal growth factor EGF. Then, we developed Vi-Fi scoring—a novel drug repurposing approach and simultaneously quantified antiviral and antifibrotic activities of the drugs based on their transcriptomic signatures. We revealed the strong dual antifibrotic and antiviral activity of EGFR/ErbB inhibitors. Before the in vitro validation, we have clustered 277 cell lines and revealed distinct COVID-19 transcriptomic signatures of the cells with similar phenotypes that defines their suitability for COVID-19 research. By ERK activity monitoring in living lung cells, we show that the drugs with predicted antifibrotic activity downregulate ERK in the host lung cells. Overall, our study provides novel insights on SARS-CoV-2 dependence on EGFR/ERK signaling and demonstrates the utility of EGFR/ErbB inhibitors for COVID-19 treatment.Elmira R. VagapovaTimofey D. LebedevVladimir S. PrassolovNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elmira R. Vagapova Timofey D. Lebedev Vladimir S. Prassolov Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
description	Abstract Understanding the molecular basis of fibrosis, the lethal complication of COVID-19, is urgent. By the analysis of RNA-sequencing data of SARS-CoV-2-infected cells combined with data mining we identified genes involved in COVID-19 progression. To characterize their implication in the fibrosis development we established a correlation matrix based on the transcriptomic data of patients with idiopathic pulmonary fibrosis. With this method, we have identified a cluster of genes responsible for SARS-CoV-2-fibrosis including its entry receptor ACE2 and epidermal growth factor EGF. Then, we developed Vi-Fi scoring—a novel drug repurposing approach and simultaneously quantified antiviral and antifibrotic activities of the drugs based on their transcriptomic signatures. We revealed the strong dual antifibrotic and antiviral activity of EGFR/ErbB inhibitors. Before the in vitro validation, we have clustered 277 cell lines and revealed distinct COVID-19 transcriptomic signatures of the cells with similar phenotypes that defines their suitability for COVID-19 research. By ERK activity monitoring in living lung cells, we show that the drugs with predicted antifibrotic activity downregulate ERK in the host lung cells. Overall, our study provides novel insights on SARS-CoV-2 dependence on EGFR/ERK signaling and demonstrates the utility of EGFR/ErbB inhibitors for COVID-19 treatment.
format	article
author	Elmira R. Vagapova Timofey D. Lebedev Vladimir S. Prassolov
author_facet	Elmira R. Vagapova Timofey D. Lebedev Vladimir S. Prassolov
author_sort	Elmira R. Vagapova
title	Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
title_short	Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
title_full	Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
title_fullStr	Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
title_full_unstemmed	Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis
title_sort	viral fibrotic scoring and drug screen based on mapk activity uncovers egfr as a key regulator of covid-19 fibrosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/af657faedb774b16b9c79f1776b9032d
work_keys_str_mv	AT elmirarvagapova viralfibroticscoringanddrugscreenbasedonmapkactivityuncoversegfrasakeyregulatorofcovid19fibrosis AT timofeydlebedev viralfibroticscoringanddrugscreenbasedonmapkactivityuncoversegfrasakeyregulatorofcovid19fibrosis AT vladimirsprassolov viralfibroticscoringanddrugscreenbasedonmapkactivityuncoversegfrasakeyregulatorofcovid19fibrosis
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Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis

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