Identification of novel small chemical compounds that inhibit Ebola virus VP40-mediated virus-like particle production.

The central role of Ebola virus (EBOV) VP40 in nascent virion assembly and budding from infected host cells makes it an important therapeutic target. Previously, we reported two novel chemical compounds (NUSU#1 and NUSU#2) that inhibit EBOV VP40-mediated virus-like particle (VLP) production. In this study, we aimed to develop and identify novel synthetic compounds derived from NUSU#1. Forty-five compounds were synthesized and examined for their effects in vitro. Through cell viability and screening assays that we previously developed and reported, five novel synthesized compounds were selected for their inhibitory effects on EBOV VP40-mediated VLP production. Although none of them showed a stronger inhibitory effect on VLP production than NUSU#1, four of the five selected compounds exhibited a statistically significant reduction in EBOV VP40-mediated VLP production compared with the control treatment using a VLP assay.