Screening of FDA-approved drugs using a recombinant Cedar virus to improve treatment options for Nipah virus infection

Nipah virus and Hendra virus are highly pathogenic henipaviruses for which there are no approved therapeutics for use in humans. Using recombinant Cedar virus expressing luciferase (rCedV-Luc) as a CL2 surrogate, we screened a library of 2,703 Food and Drug Administration (FDA)-approved compounds, yielding 5 promising candidates: bortezomib, harringtonine, homoharringtonine, ixazomib citrate and lanatoside C. Compounds demonstrated low half-maximal inhibitory concentration (IC 50 ) values of ≤0.45 µM and high selectivity indexes >6 in mammalian cell lines. Time-of-addition studies suggest that these compounds target a post-entry stage of henipavirus replication. This study demonstrates the utility of rCedV-Luc as a surrogate for the antiviral screening of henipaviruses and identification of promising candidates for further investigation and development as henipavirus antivirals.