viruses Article Identification of Novel Antiviral Compounds Targeting Entry of Hantaviruses Jennifer Mayor 1,2, Giulia Torriani 1,2, Olivier Engler 2 and Sylvia Rothenberger 1,2,* 1 Institute of Microbiology, University Hospital Center and University of Lausanne, Rue du Bugnon 48, CH-1011 Lausanne, Switzerland;
[email protected] (J.M.);
[email protected] (G.T.) 2 Spiez Laboratory, Swiss Federal Institute for NBC-Protection, CH-3700 Spiez, Switzerland;
[email protected] * Correspondence:
[email protected]; Tel.: +41-21-314-51-03 Abstract: Hemorrhagic fever viruses, among them orthohantaviruses, arenaviruses and filoviruses, are responsible for some of the most severe human diseases and represent a serious challenge for public health. The current limited therapeutic options and available vaccines make the development of novel efficacious antiviral agents an urgent need. Inhibiting viral attachment and entry is a promising strategy for the development of new treatments and to prevent all subsequent steps in virus infection. Here, we developed a fluorescence-based screening assay for the identification of new antivirals against hemorrhagic fever virus entry. We screened a phytochemical library containing 320 natural compounds using a validated VSV pseudotype platform bearing the glycoprotein of the virus of interest and encoding enhanced green fluorescent protein (EGFP). EGFP expression allows the quantitative detection of infection and the identification of compounds affecting viral entry. We identified several hits against four pseudoviruses for the orthohantaviruses Hantaan (HTNV) and Citation: Mayor, J.; Torriani, G.; Andes (ANDV), the filovirus Ebola (EBOV) and the arenavirus Lassa (LASV). Two selected inhibitors, Engler, O.; Rothenberger, S.