{Reference Type}: Journal Article
{Title}: ML241 Antagonizes ERK 1/2 Activation and Inhibits Rotavirus Proliferation.
{Author}: Wang J;Hu X;Wu J;Lin X;Chen R;Lu C;Song X;Leng Q;Li Y;Kuang X;Li J;Yao L;Tang X;Ye J;Zhang G;Sun M;Zhou Y;Li H;
{Journal}: Viruses
{Volume}: 16
{Issue}: 4
{Year}: 2024 04 17
{Factor}: 5.818
{DOI}: 10.3390/v16040623
{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.