Cusculine

Cusculine (FAC21) is an oropouche virus (OROV) endonuclease inhibitor with an IC₅₀ of 1.4 μM. Cusculine strongly interacts with OROV endonuclease, possibly limiting viral RNA interaction with other proteins, intercalates into double-stranded RNA (a viral replication intermediate), and efficiently inhibits OROV viral replication in vitro. Cusculine can be used for the research of oropouche fever ^[1].

In Vitro, Cusculine (FAC21) (72 h) exhibits low cytotoxicity in Vero cells (CC50 = 1640 μM)^[1]. Cusculine (15.125-250 μM) potently inhibits OROV infection in Vero cells (EC50 = 33.03 μM)^[1]. Cusculine (125 μM; 8-48 hpi) strongly inhibits OROV replication early in Vero cells (99.9% inhibition at 8 hpi)^[1]. Cusculine (18.5 μM; 45 min) modestly interacts with dsRNA, showing partial intercalation activity^[1]. Cusculine (0-90 μM; 10 min) potently inhibits OROV N-terminal endonuclease as a competitive inhibitor (IC₅₀ = 1.4 μM)^[1]. Cusculine stably binds to the active site of OROV N-terminal endonuclease, with favorable binding free energy and conserved interacting residues^[1].

References:
[1]. Saivish MV, et al. Acridones as promising drug candidates against Oropouche virus. Curr Res Microb Sci. 2023;6:100217. Published 2023 Dec 23.