KDM5 Family Demethylase Inhibitor KDOAM-25 Reduces Entry of SARS-CoV-2 Pseudotyped Viral Particles into Cells

We studied the effect of KDM5 family demethylase inhibitors (JIB-04, PBIT, and KDOAM-25) on the penetration of SARS-CoV-2 pseudotyped viruses into differentiated Caco-2 cells and HEK293T cells withACE2 hyperexpression. The above drugs were not cytotoxic. Only KDOAM-25 significantly reduced virus entry into the cells. The expression ofACE2 mRNA in Caco-2 significantly increased, whileTMPRSS2 expression did not significantly change under these conditions. In differentiated Caco-2 cells, KDOAM-25 did not affect the expression ofBRCA1,CDH1,TP53,SNAI1,VIM, andUGCG genes, for which an association with knockdown or overexpression of KDM5 demethylases or with the action of demethylase inhibitors had previously been shown. In undifferentiated Caco-2 cells, the expression ofBRCA1,SNAI1,VIM, andCDH1 was significantly increased under the action of KDOAM-25.

Source: Bulletin of Experimental Biology and Medicine - June 19, 2023 Category: Biology Source Type: research