Parallel compound screen for infection modulators identifies re-purposing candidates against common viral infections
Viral infectious diseases span a myriad of maladies, including immunosuppression, cancer, organ failure and, if lacking effective treatment, even death. While numerous targeted antiviral therapies have been developed over the past century, many viral diseases still lack effective antivirals to date. Revisiting compounds approved for other applications offers accelerated development, and automated screening and data processing boost the feasibility of the re-purposing approach. Here, we extended our high-content image-based platform on three human viruses differing in genome composition, envelope state, and tropism, namely human rhinovirus (RV), influenza A virus (IAV) and herpes simplex virus (HSV). Among the 1,280 mainly FDA-approved compounds, we identified potent inhibitors and even enhancers of multi-round infection propagation in vitro. The most potent inhibitors were 5-azacytidin against RV-A16, clotrimazole against IAV-WSN, and raltitrexed against HSV-1. Clobetasol was found to significantly enhance HSV-1 infection. Remarkably, Aminacrine, a topical antiseptic, inhibited all three viruses tested. Follow-up experiments of the highest-scoring modulators confirmed their performance.
Olszewski D, Georgi F, Murer L, Andriasyan V, Kuttler F, Witte R, Yakimovich A, Rozanova A, Yamauchi Y, Turcatti G, Greber UF
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Copyright: Olszewski et al
Data Publisher: University of Dundee
