M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Faculty of Biology and Biotechnologies, National Research University Higher School of Economics, Moscow, Russia.
Bull Exp Biol Med. 2023 May;175(1):150-156. doi: 10.1007/s10517-023-05827-w. Epub 2023 Jun 19.
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 virus entry into the cells. The expression of ACE2 mRNA in Caco-2 significantly increased, while TMPRSS2 expression did not significantly change under these conditions. 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 with the action of demethylase inhibitors had previously been shown. In undifferentiated Caco-2 cells, the expression of BRCA1, SNAI1, VIM, and CDH1 was significantly increased under the action of KDOAM-25.
我们研究了 KDM5 家族去甲基化酶抑制剂（JIB-04、PBIT 和 KDOAM-25）对 SARS-CoV-2 假型病毒进入过表达 ACE2 的分化 Caco-2 细胞和 HEK293T 细胞的影响。上述药物没有细胞毒性。只有 KDOAM-25 显著降低了病毒进入细胞的水平。在这些条件下，Caco-2 中的 ACE2 mRNA 表达显著增加，而 TMPRSS2 表达没有显著变化。在分化的 Caco-2 细胞中，KDOAM-25 不影响 BRCA1、CDH1、TP53、SNAI1、VIM 和 UGCG 基因的表达，先前已经表明这些基因与 KDM5 去甲基酶的敲低或过表达或去甲基酶抑制剂的作用有关。在未分化的 Caco-2 细胞中，KDOAM-25 的作用下 BRCA1、SNAI1、VIM 和 CDH1 的表达显著增加。
