Ингибитор деметилаз семейства KDM5 — KDOAM-25 — снижает проникновение псевдотипированных вирусных частиц SARS-CoV-2 в клетки
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 with ACE2 hyperexpression. The above drugs were not cytotoxic. Only KDOAM-25 significantly reduced viral entry into cells. At the same time, the level of ACE2 mRNA expression in Caco-2 significantly increased, while TMPRSS2 expression did not significantly change. In differentiated Caco-2 cells KDOAM-25 did not affect the expression of BRCA1, CDH1, TP53, SNAI1, VIM, and UGCG genes, for which an association with knockdown or overexpression of KDM5 demethylases or the action of demethylase inhibitors had previously been shown. However, BRCA1, SNAI1, VIM, and CDH1 expression was significantly increased in undifferentiated Caco-2 cells under the action of KDOAM-25.