TY - JOUR
T1 - Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1
AU - Lee, Ahrim
AU - Sung, Jieun
AU - Harmalkar, Dipesh S.
AU - Kang, Hyeseul
AU - Lee, Hwayoung
AU - Lee, Kyeong
AU - Lee, Choongho
N1 - Publisher Copyright:
© 2022 The Korean Society of Applied Pharmacology.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
KW - Antiviral mechanism of action
KW - Heat shock factor-1
KW - Norovirus
KW - RNA replication inhibitor
KW - Vinyl-stilbene
UR - http://www.scopus.com/inward/record.url?scp=85122927470&partnerID=8YFLogxK
U2 - 10.4062/biomolther.2021.153
DO - 10.4062/biomolther.2021.153
M3 - Article
AN - SCOPUS:85122927470
SN - 1976-9148
VL - 30
SP - 64
EP - 71
JO - Biomolecules and Therapeutics
JF - Biomolecules and Therapeutics
IS - 1
ER -
