tetano
Editor, Senior Moderator
Sci Rep
. 2021 Sep 17;11(1):18581.
doi: 10.1038/s41598-021-97972-3.
Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
Takeshi Yamamotoya[SUP] #[/SUP][SUP] 1 [/SUP], Yusuke Nakatsu[SUP] #[/SUP][SUP] 1 [/SUP], Machi Kanna[SUP] 1 [/SUP], Shun Hasei[SUP] 1 [/SUP], Yukino Ohata[SUP] 1 [/SUP], Jeffrey Encinas[SUP] 2 [/SUP], Hisanaka Ito[SUP] 3 [/SUP], Takayoshi Okabe[SUP] 4 [/SUP], Tomoichiro Asano[SUP] 5 [/SUP], Takemasa Sakaguchi[SUP] 6 [/SUP]
Affiliations
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 EC[SUB]50[/SUB] 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.
. 2021 Sep 17;11(1):18581.
doi: 10.1038/s41598-021-97972-3.
Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
Takeshi Yamamotoya[SUP] #[/SUP][SUP] 1 [/SUP], Yusuke Nakatsu[SUP] #[/SUP][SUP] 1 [/SUP], Machi Kanna[SUP] 1 [/SUP], Shun Hasei[SUP] 1 [/SUP], Yukino Ohata[SUP] 1 [/SUP], Jeffrey Encinas[SUP] 2 [/SUP], Hisanaka Ito[SUP] 3 [/SUP], Takayoshi Okabe[SUP] 4 [/SUP], Tomoichiro Asano[SUP] 5 [/SUP], Takemasa Sakaguchi[SUP] 6 [/SUP]
Affiliations
- PMID: 34535740
- DOI: 10.1038/s41598-021-97972-3
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 EC[SUB]50[/SUB] 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.