Biomol Ther.  2022 Jan;30(1):64-71. 10.4062/biomolther.2021.153.

Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1

• Lee A
• Sung J
• Harmalkar DS
• Kang H
• Lee H
• Lee K
• Lee C

• KMID: 2524148
• DOI: http://doi.org/10.4062/biomolther.2021.153

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 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.

Keyword

Norovirus; Vinyl-stilbene; RNA replication inhibitor; Heat shock factor-1; Antiviral mechanism of action