Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target
| العنوان: | Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target |
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| المؤلفون: | Hisanaka Ito, Tomoichiro Asano, Machi Kanna, Takayoshi Okabe, Jeffrey Encinas, Takemasa Sakaguchi, Shun Hasei, Yusuke Nakatsu, Yukino Ohata, Takeshi Yamamotoya |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Acute promyelocytic leukemia, viruses, Science, Retinoic acid, Drug development, Virus Replication, Article, chemistry.chemical_compound, Target identification, Chlorocebus aethiops, Prolyl isomerase, medicine, Animals, Gene silencing, Pandemics, Vero Cells, Cytopathic effect, Multidisciplinary, SARS-CoV-2, Chemistry, COVID-19, Virus Internalization, medicine.disease, NIMA-Interacting Peptidylprolyl Isomerase, Retinoic acid receptor, Viral replication, Cancer research, PIN1, Infectious diseases, Medicine |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e87c15701fde03b4edbdf803cad0b49d https://doaj.org/article/1ea816cff4094d0dadc3628615db9c97 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e87c15701fde03b4edbdf803cad0b49d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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