ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2 Author links open overlay panel
Date
2023
Authors
Demian, Wael L.
Jacob, Rajesh Abraham
Cormier, Olga
Nazli, Aisha
Melki, Matthew
Asavajaru, Akarin
Baid, Kaushal
Zhang, Ali
Miller, Matthew S.
Kaushic, Charu
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Elsevier
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Article
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Abstract
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 N-terminal 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.
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Keywords
Antiviral, SARS-CoV-2, ASK1, Vesicular stomatitis virus, Herpes simplex virus, Selonsertib
Citation
Demian, W. L., Jacob, R. A., Cormier, O., Nazli, A., Melki, M., Asavajaru, A., Baid, K., Zhang, A., Miller, M. S., Kaushic, C., Banerjee, A., & Mossman, K. (2023). ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2. Antiviral Research, 220, Article 105736. https://doi.org/10.1016/j.antiviral.2023.105736
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DOI
https://doi.org/10.1016/j.antiviral.2023.105736