Journal
ANTIVIRAL RESEARCH
Volume 220, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2023.105736
Keywords
Antiviral; SARS-CoV-2; ASK1; Vesicular stomatitis virus; Herpes simplex virus; Selonsertib
Categories
Ask authors/readers for more resources
The study found that virus infection activates ASK1-related pathways, and the ASK1 inhibitor Selonsertib significantly reduces the replication of various viruses in human cell lines. However, differential effects of Selonsertib were observed in in vitro and in vivo hamster models, suggesting caution in predicting clinical and therapeutic outcomes in humans using rodent models.
Apoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun Nterminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/ p38MAPK or ASK1/JNK pathways. Our findings suggest that virus infection activates ASK1 related pathways. In parallel, ASK1 inhibition led to a remarkable reduction in the replication of a broad range of viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccinia virus (VV), vesicular stomatitis virus (VSV), Herpes Simplex Virus (HSV), and Human Immunodeficiency virus (HIV) in different human cell lines. Our work demonstrates the potential therapeutic use of Selonsertib, an ASK1 inhibitor, as a pan-antiviral drug in humans. Surprisingly, we observed differential effects of Selonsertib in in vitro and in vivo hamster models, suggesting caution in using rodent models to predict clinical and therapeutic outcomes in humans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available