학술논문

ML241 Antagonizes ERK 1/2 Activation and Inhibits Rotavirus Proliferation.
Document Type
Article
Source
Viruses (1999-4915). Apr2024, Vol. 16 Issue 4, p623. 15p.
Subject
*ROTAVIRUSES
*CYTOTOXINS
*CELLULAR signal transduction
*DRUG development
*LABORATORY mice
*MITOGEN-activated protein kinases
Language
ISSN
1999-4915
Abstract
Rotavirus (RV) is the main pathogen that causes severe diarrhea in infants and children under 5 years of age. No specific antiviral therapies or licensed anti-rotavirus drugs are available. It is crucial to develop effective and low-toxicity anti-rotavirus small-molecule drugs that act on novel host targets. In this study, a new anti-rotavirus compound was selected by ELISA, and cell activity was detected from 453 small-molecule compounds. The anti-RV effects and underlying mechanisms of the screened compounds were explored. In vitro experimental results showed that the small-molecule compound ML241 has a good effect on inhibiting rotavirus proliferation and has low cytotoxicity during the virus adsorption, cell entry, and replication stages. In addition to its in vitro effects, ML241 also exerted anti-RV effects in a suckling mouse model. Transcriptome sequencing was performed after adding ML241 to cells infected with RV. The results showed that ML241 inhibited the phosphorylation of ERK1/2 in the MAPK signaling pathway, thereby inhibiting IκBα, activating the NF-κB signaling pathway, and playing an anti-RV role. These results provide an experimental basis for specific anti-RV small-molecule compounds or compound combinations, which is beneficial for the development of anti-RV drugs. [ABSTRACT FROM AUTHOR]