High-throughput drug screening using the Ebola virus transcription- and replication-competent virus-like particle system

Antiviral Research
Nakyung LeeMarc P Windisch

Abstract

The massive epidemic of Ebola virus disease (EVD) in West Africa, followed in recent months by two outbreaks in the Democratic Republic of the Congo, underline the importance of this severe disease. Because Ebola virus (EBOV) must be manipulated under biosafety level 4 (BSL4) containment, the discovery and development of virus-specific therapies have been hampered. Recently, a transient transfection-based transcription- and replication competent virus-like particle (trVLP) system was described, enabling modeling of the entire EBOV life cycle under BSL2 conditions. Using this system, we optimized the condition for bulk co-transfection of multiple plasmids, developed a luciferase reporter-based assay in 384-well microtiter plates, and performed a high-throughput screening (HTS) campaign of an 8,354-compound collection consisting of U.S. Food & Drug Administration (FDA) -approved drugs, bioactives, kinase inhibitors, and natural products in duplicates. The HTS achieved a good signal-to-background ratio with a low percent coefficient of variation resulting in Z' = 0.7, and data points were reproducible with R2 = 0.89, indicative of a robust assay. After applying stringent hit selection criteria of ≥70% EBOV trVLP inhibition and ≥70...Continue Reading

Citations

Apr 25, 2019·The Journal of General Virology·Lennart KämperThomas Hoenen
Mar 22, 2019·Viruses·Cristiano SalataGiorgio Palù
Jun 13, 2020·F1000Research·Shawn GoyalDonald R Branch
Jul 26, 2019·Nature Reviews. Microbiology·Thomas HoenenHeinz Feldmann
Feb 26, 2021·Scientific Reports·Sinead M O'DonovanRobert E McCullumsmith
Dec 6, 2018·ACS Infectious Diseases·Elena K Schneider-FutschikTony Velkov

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