Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP.
Enteroviruses, e.g., polio-, coxsackie- and rhinoviruses, constitute a large genus within the Picornaviridae family of positive-strand RNA viruses and include many important pathogens linked to a variety of acute and chronic diseases. Despite their huge medical and economic impact, no approved antiviral therapy is yet available. Recently, the oxysterol-binding protein (OSBP) was implicated as a host factor for enterovirus replication. Here, we investigated the antiviral activity of the natural compound OSW-1, a ligand of OSBP that is under investigation as an anti-cancer drug. OSW-1 potently inhibited the replication of all enteroviruses tested, with IC50 values in the low nanomolar range, acted at the genome replication stage and was effective in all tested cell types of three different species. Importantly, OSBP overexpression rescued viral replication, demonstrating that the antiviral effect of OSW-1 is due to targeting OSBP. Together, we here report the anti-enterovirus activity of the natural anti-cancer compound OSW-1.
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Lucian
L
Albulescu
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Jeroen R P M
JR
Strating
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Hendrik Jan
HJ
Thibaut
Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
Lonneke
L
van der Linden
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, USA.
Matthew D
MD
Shair
Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Johan
J
Neyts
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: F.J.M.vanKuppeveld@uu.nl.
Frank J M
FJ
van Kuppeveld
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002783:Cholestenones / Q000494:pharmacology*; D004770:Enterovirus / Q000187:drug effects* / Q000254:growth & development; D016679:Genome, Viral / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D011987:Receptors, Steroid / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014709:Vero Cells; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*; D000098825:Oxysterol Binding Proteins
D000998:Antiviral Agents; D002783:Cholestenones; D008024:Ligands; D011987:Receptors, Steroid; D012503:Saponins; D000098825:Oxysterol Binding Proteins; C106408:OSW 1
Antiviral; Coxsackievirus; Enterovirus; Oxysterol-binding protein; Replication