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http://dx.doi.org/10.4062/biomolther.2021.153

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)
Publication Information
Biomolecules & Therapeutics / v.30, no.1, 2022 , pp. 64-71 More about this Journal
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
Norovirus; Vinyl-stilbene; RNA replication inhibitor; Heat shock factor-1; Antiviral mechanism of action;
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