Quantitative proteomic analysis of the tizoxanide effect in vero cells

Abstract Nitazoxanide (NTZ) is effective against helminths and numerous microorganisms, including bacteria and viruses. In vivo, NTZ is metabolized into Tizoxanide (TIZ), which is the active circulating metabolite. With the emergence of SARS-Cov-2 as a Pandemic agent, NTZ became one of the molecules...

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Autores principales:	K. A. Yamamoto, K. Blackburn, E. Migowski, M. B. Goshe, D. T. Brown, D. F. Ferreira, M. R. Soares
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/974c4c445a274060affb622b8dcbc153
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spelling	oai:doaj.org-article:974c4c445a274060affb622b8dcbc1532021-12-02T19:12:33ZQuantitative proteomic analysis of the tizoxanide effect in vero cells10.1038/s41598-020-71634-22045-2322https://doaj.org/article/974c4c445a274060affb622b8dcbc1532020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71634-2https://doaj.org/toc/2045-2322Abstract Nitazoxanide (NTZ) is effective against helminths and numerous microorganisms, including bacteria and viruses. In vivo, NTZ is metabolized into Tizoxanide (TIZ), which is the active circulating metabolite. With the emergence of SARS-Cov-2 as a Pandemic agent, NTZ became one of the molecules already approved for human use to engage clinical trials, due to results in vitro showing that NTZ was highly effective against the SARS-Cov-2, agent of COVID-19. There are currently several ongoing clinical trials mainly in the USA and Brazil involving NTZ due not only to the in vitro results, but also for its long-known safety. Here, we study the response of Vero cells to TIZ treatment and unveil possible mechanisms for its antimicrobial effect, using a label-free proteomic approach (LC/MS/MS) analysis to compare the proteomic profile between untreated- and TIZ-treated cells. Fifteen differentially expressed proteins were observed related to various biological processes, including translation, intracellular trafficking, RNA processing and modification, and signal transduction. The broad antimicrobial range of TIZ points towards its overall effect in lowering cell metabolism and RNA processing and modification. The decreased levels of FASN, HNRNPH and HNRNPK with the treatment appear to be important for antiviral activity.K. A. YamamotoK. BlackburnE. MigowskiM. B. GosheD. T. BrownD. F. FerreiraM. R. SoaresNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q K. A. Yamamoto K. Blackburn E. Migowski M. B. Goshe D. T. Brown D. F. Ferreira M. R. Soares Quantitative proteomic analysis of the tizoxanide effect in vero cells
description	Abstract Nitazoxanide (NTZ) is effective against helminths and numerous microorganisms, including bacteria and viruses. In vivo, NTZ is metabolized into Tizoxanide (TIZ), which is the active circulating metabolite. With the emergence of SARS-Cov-2 as a Pandemic agent, NTZ became one of the molecules already approved for human use to engage clinical trials, due to results in vitro showing that NTZ was highly effective against the SARS-Cov-2, agent of COVID-19. There are currently several ongoing clinical trials mainly in the USA and Brazil involving NTZ due not only to the in vitro results, but also for its long-known safety. Here, we study the response of Vero cells to TIZ treatment and unveil possible mechanisms for its antimicrobial effect, using a label-free proteomic approach (LC/MS/MS) analysis to compare the proteomic profile between untreated- and TIZ-treated cells. Fifteen differentially expressed proteins were observed related to various biological processes, including translation, intracellular trafficking, RNA processing and modification, and signal transduction. The broad antimicrobial range of TIZ points towards its overall effect in lowering cell metabolism and RNA processing and modification. The decreased levels of FASN, HNRNPH and HNRNPK with the treatment appear to be important for antiviral activity.
format	article
author	K. A. Yamamoto K. Blackburn E. Migowski M. B. Goshe D. T. Brown D. F. Ferreira M. R. Soares
author_facet	K. A. Yamamoto K. Blackburn E. Migowski M. B. Goshe D. T. Brown D. F. Ferreira M. R. Soares
author_sort	K. A. Yamamoto
title	Quantitative proteomic analysis of the tizoxanide effect in vero cells
title_short	Quantitative proteomic analysis of the tizoxanide effect in vero cells
title_full	Quantitative proteomic analysis of the tizoxanide effect in vero cells
title_fullStr	Quantitative proteomic analysis of the tizoxanide effect in vero cells
title_full_unstemmed	Quantitative proteomic analysis of the tizoxanide effect in vero cells
title_sort	quantitative proteomic analysis of the tizoxanide effect in vero cells
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/974c4c445a274060affb622b8dcbc153
work_keys_str_mv	AT kayamamoto quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT kblackburn quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT emigowski quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT mbgoshe quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT dtbrown quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT dfferreira quantitativeproteomicanalysisofthetizoxanideeffectinverocells AT mrsoares quantitativeproteomicanalysisofthetizoxanideeffectinverocells
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Quantitative proteomic analysis of the tizoxanide effect in vero cells

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