Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target

Abstract Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silenc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Takeshi Yamamotoya, Yusuke Nakatsu, Machi Kanna, Shun Hasei, Yukino Ohata, Jeffrey Encinas, Hisanaka Ito, Takayoshi Okabe, Tomoichiro Asano, Takemasa Sakaguchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ea816cff4094d0dadc3628615db9c97
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1ea816cff4094d0dadc3628615db9c97
record_format	dspace
spelling	oai:doaj.org-article:1ea816cff4094d0dadc3628615db9c972021-12-02T18:50:52ZProlyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target10.1038/s41598-021-97972-32045-2322https://doaj.org/article/1ea816cff4094d0dadc3628615db9c972021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97972-3https://doaj.org/toc/2045-2322Abstract Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC50 below 5 μM regardless of whether it was added to the culture medium prior to or after SARS-CoV-2 infection. The inhibition of viral N protein mRNA synthesis by H-77 implies that the molecular mechanism underlying SARS-CoV-2 inhibition is likely to be associated with viral gene transcription or earlier steps. Another Pin1 inhibitor, all-trans retinoic acid (ATRA)—a commercially available drug used to treat acute promyelocytic leukemia (APL) and which both activates the retinoic acid receptor and inhibits the activity of Pin1—similarly reduced the proliferation of SARS-CoV-2. Taken together, the results indicate that Pin1 inhibitors could serve as potential therapeutic agents for COVID-19.Takeshi YamamotoyaYusuke NakatsuMachi KannaShun HaseiYukino OhataJeffrey EncinasHisanaka ItoTakayoshi OkabeTomoichiro AsanoTakemasa SakaguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeshi Yamamotoya Yusuke Nakatsu Machi Kanna Shun Hasei Yukino Ohata Jeffrey Encinas Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Takemasa Sakaguchi Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
description	Abstract Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells. In addition, several recently generated Pin1 inhibitors showed strong inhibitory effects on SARS-CoV-2 proliferation, measured by both viral mRNA and protein synthesis, and alleviated the cytopathic effect (CPE) on VeroE6/TMPRSS2 cells. One compound, termed H-77, was found to block SARS-CoV-2 proliferation at an EC50 below 5 μM regardless of whether it was added to the culture medium prior to or after SARS-CoV-2 infection. The inhibition of viral N protein mRNA synthesis by H-77 implies that the molecular mechanism underlying SARS-CoV-2 inhibition is likely to be associated with viral gene transcription or earlier steps. Another Pin1 inhibitor, all-trans retinoic acid (ATRA)—a commercially available drug used to treat acute promyelocytic leukemia (APL) and which both activates the retinoic acid receptor and inhibits the activity of Pin1—similarly reduced the proliferation of SARS-CoV-2. Taken together, the results indicate that Pin1 inhibitors could serve as potential therapeutic agents for COVID-19.
format	article
author	Takeshi Yamamotoya Yusuke Nakatsu Machi Kanna Shun Hasei Yukino Ohata Jeffrey Encinas Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Takemasa Sakaguchi
author_facet	Takeshi Yamamotoya Yusuke Nakatsu Machi Kanna Shun Hasei Yukino Ohata Jeffrey Encinas Hisanaka Ito Takayoshi Okabe Tomoichiro Asano Takemasa Sakaguchi
author_sort	Takeshi Yamamotoya
title	Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
title_short	Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
title_full	Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
title_fullStr	Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
title_full_unstemmed	Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
title_sort	prolyl isomerase pin1 plays an essential role in sars-cov-2 proliferation, indicating its possibility as a novel therapeutic target
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1ea816cff4094d0dadc3628615db9c97
work_keys_str_mv	AT takeshiyamamotoya prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT yusukenakatsu prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT machikanna prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT shunhasei prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT yukinoohata prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT jeffreyencinas prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT hisanakaito prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT takayoshiokabe prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT tomoichiroasano prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget AT takemasasakaguchi prolylisomerasepin1playsanessentialroleinsarscov2proliferationindicatingitspossibilityasanoveltherapeutictarget
_version_	1718377489832607744

Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target

Ejemplares similares