OSW-1

OSW-1 is a saponin that has been found in O. saundersiae and has antiviral and anticancer activities.¹ It is an inhibitor of oxysterol-binding protein (OSBP) and its paralog OSBP-related protein 4 (ORP4) with K_i values of 16 and 71 nM, respectively, in radioligand binding assays using HEK293T cell lysates.² It induces OSBP translocalization from the cytoplasm to the trans-Golgi network and decreases intracellular levels of OSBP in HEK293 cells.^2,3 OSW-1 inhibits replication of a variety of enteroviruses (IC₅₀s = 2.4-9.4 nM), including replication of coxsackievirus B3 (CVB3) in infected HeLa R19 cells in an OSBP-dependent manner when used at a concentration of 3 nM.⁴ It also inhibits replication of hepatitis C virus (HCV) but not mouse hepatitis virus (MHV), a coronavirus.⁵ It protects against CVA9 and echovirus 2 infection in HeLa cells when used at a concentration of 10 nM.⁴ OSW-1 inhibits growth of HeLa and HEK293 cells (GI₅₀s = 0.33 and 0.22 nM, respectively).²

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1. Mimaki, Y., Kuroda, M., Kameyama, A., et al. Cholestane glycosides with potent cytostatic activities on various tumor cells from Ornithogalum saundersiae bulbs. Bioorg. Med. Chem. Lett. 7(5), 633-636 (1997).

2. Roberts, B.L., Severance, Z.C., Bensen, R.C., et al. Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds. Antiviral Res. 170:104548, (2019).

3. Burgett, A.W.G., Poulsen, T.B., Wangkanont, K., et al. Natural products reveal cancer cell dependence on oxysterol-binding proteins. Nat. Chem. Biol. 7(9), 639-647 (2011).

4. Albulescu, L., Strating, J.R., Thibaut, H.J., et al. Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP. Antiviral Res. 117, 110-114 (2015).

5. Strating, J.R.P.M., van der Linden, L., Albulescu, L., et al. Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. Cell Rep. 10(4), 600-615 (2015).