| HRA013787
(Open Access)
|
In this study, we demonstrated that NVP-HSP990, a novel small-molecule heat shock protein 90 (HSP90) inhibitor, inhibited RV infection with a fascinating higher selectivity index (SI) compared to conventional HSP90 inhibitors like Geldanamycin (GA) and its derivative Tanespimycin (17-allylamino-17- demethoxygeldanamycin, 17-AAG). NVP-HSP990 effectively inhibited RV replication in vitro without blocking the initial establishment of infection. NVP-HSP990 restored host gene expression in most KEGG pathways disrupted by RV infection in Caco-2 cells except some inflammatory pathways (such as IL-17 and TNF pathways). NVP-HSP990 significantly inhibited RV-induced activation of the MAPK pathway and prevented the disruption of tight junctions in Caco-2 cells. More importantly, NVP-HSP990 effectively suppressed RV infection in BALB/c suckling mice and significantly alleviated RV-induced diarrhea. |
