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Nitazoxanide in the Treatment of COVID-19: A paradigm for Antiviral Drugs Targeting Host-Infected Cells

Brechot et al., Medical Research Archives, doi:10.18103/mra.v12i4.5252
Apr 2024  
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Review of nitazoxanide as a potential treatment for COVID-19. Authors highlight nitazoxanide's unique mechanism of action, which involves inhibiting mitochondrial oxidative phosphorylation in host cells, thereby lowering cellular ATP content and impairing viral replication and assembly, while also stimulating innate immune responses. Preclinical studies in cell culture and animal models have demonstrated nitazoxanide's ability to inhibit SARS-CoV-2 replication, including variants of concern, and to reduce disease severity. Some clinical studies show reductions in viral load, symptom duration, and disease progression, while others found no significant benefits. Authors suggest that despite the inconclusive clinical data, nitazoxanide's safety profile and host-directed mechanism warrant further investigation as a potential adjunctive therapy in combination with direct-acting antivirals, and that nitazoxanide's activity against SARS-CoV-2 may serve as a paradigm for developing host-directed antiviral drugs targeting cellular energy metabolism.
Brechot et al., 30 Apr 2024, peer-reviewed, 2 authors. Contact:
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Nitazoxanide in the Treatment of COVID-19: A paradigm for Antiviral Drugs Targeting Host-Infected Cells
Christian Brechot, Jean-Francois Rossignol
Despite significant breakthroughs in the discovery of direct-acting antivirals for several viruses, there is a need for improvement. Thus, drugs able to target host-infected cells may prove valuable in enhancing the efficacy of antivirals and avoiding resistance due to viral genetic changes. In this context, we summarize in this review the current knowledge on nitazoxanide's potential for treating COVID-19. Our review highlights nitazoxanide's very specific mode of action, targeting cellular energy through inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and stimulating the innate immune response. Thus, nitazoxanide lowers the cellular ATP content and this leads to impaired viral replication and assembly. However, since nitazoxanide only yields a mild OXPHOS inhibition, this does not affect cell viability. Preclinical results and some clinical studies have suggested that nitazoxanide might be helpful for treating COVID-19. Indeed, some clinical studies have shown a decrease in severe COVID19 evolution as well as in viral multiplication; yet the results are still debated. Overall, the available information suggests the potential of nitazoxanide in association with direct-acting antivirals. In fact, this may hold true for other viruses than SARS-CoV-2 in the future. The impact of nitazoxanide on COVID-19 should be viewed as a paradigm for antiviral drugs targeting host-infected cells, and nitazoxanide should be part of the therapeutic tools for future emerging virus-related pandemics. Nitazoxanide in the Treatment of COVID-19
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