Study of gonadal hormone drugs in blocking filovirus entry of cells in vitro / 药学学报

ABSTRACT

This study was designed to discover filovirus entry inhibitors in a drug library of commercial medicines. One thousand and six hundred drugs were screened using the ZEBOV-GP/HIV model, a pseudovirus formed by an HIV-core packed with the Zaire Ebola virus glycoprotein. We identified 12 gonadal hormone drugs with inhibitory activities in ZEBOV-GP/HIV entry at final concentration of 10 μmol x L(-1). Among them, three drugs exhibited strong activities with IC50 < 1 μmol x L(-1), such as toremifene citrate (IC50 0.19 ± 0.02 μmol x L(-1)), tamoxifen citrate (IC50 0.32 ± 0.01 μmol x L(-1)) and clomiphene citrate (IC50 0.53 ± 0.02 μmol x L(-1)); seven drugs had moderate activities with IC50 between 1 and 10 μmol x L(-1), such as estradiol benzoate (IC50 1.83 ± 5.69 μmol x L(-1)), raloxifene hydrochloride (IC50 3.48 ± 0.07 μmol x L(-1)), equilin (IC50 4.00 ± 9.94 μmol x L(-1)), estradiol (IC50 5.26 ± 9.92 μmol x L(-1)), quinestrol (IC50 6.36?5.37 gmol-L1), estrone (IC50 6.87 ± 0.03 μmol-L1) and finasteride (IC50 9.94 ± 0.45 μmol x L(-1)); two drugs, hexestrol (IC50 14.20 ± 0.55 μmol x L(-1)) and chlormadinone acetate (IC50 24.60 ± 0.36 μmol x L(-1)), had weak activities against ZEBOV. Further, toremifene citrate, tamoxifen citrate, clomiphene citrate, raloxifene hydrochloride and quinestrol could block both pseudovirus type Sudan ebola virus (SEBOV-GP/HIV) and Marburg virus (MARV-GP/HIV) entries.