Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1

  • Lee, Ahrim (College of Pharmacy, Dongguk University-Seoul) ;
  • Sung, Jieun (College of Pharmacy, Dongguk University-Seoul) ;
  • Harmalkar, Dipesh S. (College of Pharmacy, Dongguk University-Seoul) ;
  • Kang, Hyeseul (College of Pharmacy, Dongguk University-Seoul) ;
  • Lee, Hwayoung (College of Pharmacy, Dongguk University-Seoul) ;
  • Lee, Kyeong (College of Pharmacy, Dongguk University-Seoul) ;
  • Lee, Choongho (College of Pharmacy, Dongguk University-Seoul)
  • Received : 2021.09.28
  • Accepted : 2021.10.25
  • Published : 2022.01.01
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Abstract

Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic sub-cellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2019R1F1A1058628). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-2018R1A5A2023127).

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