Antiviral effect of thiazolides relies on mitochondrial mild uncoupling

Abstract

BackgroundViruses are dependent on cellular energy metabolism for their replication, the drug Nitazoxanide (Alinia) was shown to interfere with both. An effect of Alinia on cellular energy metabolism is the uncoupling of mitochondrial oxidative phosphorylation (OXPHOS). Our hypothesis was that uncoupling grounds the antiviral properties of Alinia. MethodsAlinia or an unrelated uncoupler were applied to a viral releasing cell line to obtain the same increasing levels of uncoupling hence identical interference with OXPHOS. FindingsDecrease in infectious viral particles release reflected the intensity of interference irrespective of the nature of the drug and was significant with modest deviation ([≤]25%) from normal. InterpretationsA mild interference on cellular energy metabolism impacts significantly on viral replication cycle. This would explain Alinias antiviral properties in vitro moreover antiviral action of Alinia is supported by clinical trials. PerspectivesAltogether this indicates that moderate interference with mitochondrial bioenergetics should be considered as a ground for a therapeutic effect. In addition, Alinia would constitute example for a safe therapeutical use of an uncoupler, which deserves consideration for a wider range of applications.