Study of gonadal hormone drugs in blocking filovirus entry of cells in vitro

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 10μmol·L^-1. Among them, three drugs exhibited strong activities with IC₅₀< 1μmol·L^-1, such as toremifene citrate(IC₅₀:0.19±0.02μmol·L^-1), tamoxifen citrate(IC₅₀:0.32±0.01μmol·L^-1) and clomiphene citrate(IC₅₀:0.53±0.02μmol·L^-1); seven drugs had moderate activities with IC₅₀ between 1 and 10μmol·L^-1, such as estradiol benzoate(IC₅₀:1.83±5.69μmol·L^-1), raloxifene hydrochloride(IC₅₀:3.48±0.07μmol·L^-1), equilin(IC₅₀:4.00±9.94μmol·L^-1), estradiol(IC₅₀:5.26±9.92μmol·L^-1), quinestrol(IC₅₀:6.36±5.37μmol·L^-1), estrone(IC₅₀:6.87±0.03μmol·L^-1) and finasteride(IC₅₀:9.94±0.45μmol·L^-1); two drugs, hexestrol(IC₅₀:14.20±0.55μmol·L^-1) and chlormadinone acetate(IC₅₀:24.60±0.36μmol·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.