Fig. 1. High-throughput screen of anithistamine library.

(a) Antihistamines represent a potential reservoir for anti-filovirus drug development. A category analysis of drugs from Prestwick library shows 9 out of 34 histamine H1 receptor antagonists exhibit inhibitory activity against filovirus infection. (b) An antihistamine chemical library of 1220 compounds was screened against pseudotypted MARV and LASV at a final compound concentration of 6.25 μg/mL. Fifty compounds showing >80% inhibition against MARV and <30% inhibition against LASV were picked up for confirmation. The filovirus specific hits were further validated by various pseudovirions including HIV/EBOV, HIV/MARV, HIV/LASV and HIV/AIV. The top 27 filovirus-specific hits were further evaluated by dose-response titrations for both pseudotyped filovirus infection and cell toxicity. Twelve compounds with IC₅₀<10 μM, SI>10 were selected for authentic filovirus validation. (c) Top 12 hits specifically inhibit entry of pseudovirions HIV/EBOV and HIV/MARV but not HIV/LASV and HIV/AIV at 6.25 μg/mL. Data are means ± SEM from three independent experiments for HIV/EBOV, HIV/MARV and HIV/LASV (n = 3); data are mean for HIV/AIV from one experiment (n = 1). The statistical analysis is reported in Supplementary Table 2.