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Antiviral effect of thiazolides relies on mitochondrial mild uncoupling

bioRxiv, ISSN: 2692-8205
2022
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Article Description

Background: Viruses 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. Methods: Alinia 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. Findings: Decrease 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. Interpretations: A mild interference on cellular energy metabolism impacts significantly on viral replication cycle. This would explain antiviral properties in vitro moreover antiviral action of Alinia is supported by clinical trials. Perspectives: Altogether 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.

Bibliographic Details

Noureddine Hammad; Céline Ransy; Jeremy Talmasson; Frédéric Bouillaud; Benoit Pinson; Christian Bréchot; Jean François Rossignol

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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