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KMID : 0606920220300010064
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Biomolecules & Therapeutics
2022 Volume.30 No. 1 p.64 ~ p.71
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Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1
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Lee Ah-Rim
Sung Ji-Eun
Harmalkar Dipesh S.
Kang Hye-Seul
Lee Hwa-Young
Lee Kyeong
Lee Choong-Ho
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Abstract
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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 subcellular 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.
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KEYWORD
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Norovirus, Vinyl-stilbene, RNA replication inhibitor, Heat shock factor-1, Antiviral mechanism of action
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