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

Takeshi Yamamotoya1, Yusuke Nakatsu1, Machi Kanna1

  • 1Department of Medical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Scientific Reports
|September 18, 2021
PubMed

Insights

Pin1 is essential for SARS-CoV-2 replication. Inhibiting Pin1 with compounds like H-77 and ATRA significantly reduced viral proliferation and cytopathic effects, suggesting Pin1 inhibitors as potential COVID-19 therapeutics.

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates novel therapeutic strategies.
  • Cellular factors involved in viral propagation are potential drug targets.

Purpose of the Study:

  • To investigate the role of the peptidyl-prolyl isomerase Pin1 in SARS-CoV-2 replication.
  • To evaluate the efficacy of Pin1 inhibitors as potential antiviral agents against SARS-CoV-2.

Main Methods:

  • siRNA-mediated silencing of Pin1 expression in VeroE6/TMPRSS2 cells.
  • Treatment with Pin1 inhibitors (H-77 and ATRA) to assess SARS-CoV-2 proliferation.
  • Measurement of viral mRNA and protein synthesis, and cytopathic effect (CPE).

Main Results:

  • Silencing Pin1 significantly suppressed SARS-CoV-2 proliferation.
  • Pin1 inhibitors H-77 and ATRA demonstrated strong inhibitory effects on viral replication.
  • H-77 inhibited viral N protein mRNA synthesis, suggesting interference with transcription or earlier steps.
  • ATRA, a drug for acute promyelocytic leukemia, also reduced SARS-CoV-2 proliferation.

Conclusions:

  • Pin1 is a critical host factor for SARS-CoV-2 propagation.
  • Pin1 inhibitors show promise as a new class of antiviral therapeutics for COVID-19.

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