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ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2.
Demian, Wael L; Jacob, Rajesh Abraham; Cormier, Olga; Nazli, Aisha; Melki, Matthew; Asavajaru, Akarin; Baid, Kaushal; Zhang, Ali; Miller, Matthew S; Kaushic, Charu; Banerjee, Arinjay; Mossman, Karen.
Afiliação
  • Demian WL; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Jacob RA; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Cormier O; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Nazli A; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Melki M; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • Asavajaru A; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.
  • Baid K; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.
  • Zhang A; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • Miller MS; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
  • Kaushic C; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
  • Banerjee A; Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada; Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.
  • Mossman K; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Scien
Antiviral Res ; 220: 105736, 2023 12.
Article em En | MEDLINE | ID: mdl-37863359
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / COVID-19 Limite: Humans Idioma: En Revista: Antiviral Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / COVID-19 Limite: Humans Idioma: En Revista: Antiviral Res Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá