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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2020-09-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-020-71634-2 |
id |
doaj-974c4c445a274060affb622b8dcbc153 |
---|---|
record_format |
Article |
spelling |
doaj-974c4c445a274060affb622b8dcbc1532021-09-12T11:19:57ZengNature Publishing GroupScientific Reports2045-23222020-09-0110111010.1038/s41598-020-71634-2Quantitative proteomic analysis of the tizoxanide effect in vero cellsK. A. Yamamoto0K. Blackburn1E. Migowski2M. B. Goshe3D. T. Brown4D. F. Ferreira5M. R. Soares6Department of Biochemistry, Institute of Chemistry, Federal University of Rio de JaneiroDepartment of Molecular and Structural Biochemistry, North Carolina State UniversityInstitute of Pediatrics and Puericulture Martagão Gesteira, Federal University of Rio de JaneiroDepartment of Molecular and Structural Biochemistry, North Carolina State UniversityDepartment of Molecular and Structural Biochemistry, North Carolina State UniversityDepartment of Molecular and Structural Biochemistry, North Carolina State UniversityDepartment of Biochemistry, Institute of Chemistry, Federal University of Rio de JaneiroAbstract 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.https://doi.org/10.1038/s41598-020-71634-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
K. A. Yamamoto K. Blackburn E. Migowski M. B. Goshe D. T. Brown D. F. Ferreira M. R. Soares |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-09-01 |
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. |
url |
https://doi.org/10.1038/s41598-020-71634-2 |
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 |
_version_ |
1717755840691175424 |