Antifungal drug goes (anti)viral
Researchers and , part of the research group led by (Virology division, , Faculty of Veterinary Medicine) have, with international cooperation, discovered that a commonly used antifungal drug called itraconazole (ITZ) also has antiviral activity against a large group of viruses called ‘enteroviruses’, to which many clinically and economically important human and animal pathogens belong. Well-known human enteroviruses are the poliovirus (causes poliomyelitis), coxsackieviruses (myocarditis and encephalitis) and rhinoviruses (common cold).
Antitumour activity
There is a growing interest to repurpose drugs that have been used for many years and that have known to be safe. Therefore, the researchers screened a library of FDA-approved drugs for antiviral activity against enteroviruses and identified ITZ as a novel enterovirus inhibitor. ITZ counteracts fungal growth by inhibiting a fungal enzyme (CYP51) involved in the synthesis of the essential fungal membrane component ergosterol. Recently, ITZ was found to also reduce the growth of certain tumours by inhibiting angiogenesis (through inhibition of mTOR signalling and VEGFR2) and Hedgehog signalling, and it is currently in clinical trials for its antitumour activity.
Antiviral activity
Inhibition of virus replication by ITZ was not mediated by any of the known targets. Instead, the researchers identified the oxysterol-binding protein (OSBP) and the OSBP-related protein 4 (ORP4) as novel targets of ITZ. They unveiled that ITZ inhibits the activity of OSBP, i.e. transport of the lipids cholesterol and phosphatidylinositol-4-phosphate (PI4P) between cellular membranes. In infected cells, ITZ inhibited the accumulation of cholesterol on replication organelles, virus-induced structures that are essential for virus replication. A virus from another family that also depends on the activity of OSBP to generate replication organelles, the hepatitis C virus, was inhibited by ITZ as well. Whether the anticancer activity of ITZ is related to its inhibition of OSBP is unknown and remains to be determined.
An article on this research is published in the scientific journal Cell Reports.
