| Autor: |
Stachulski AV; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., Taujanskas J; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., Pate SL; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., Rajoli RKR; Department of Molecular and Clinical Pharmacology, Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K., Aljayyoussi G; Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, U.K., Pennington SH; Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, U.K., Ward SA; Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, U.K., Hong WD; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., Biagini GA; Centre for Drugs and Diagnostics, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, U.K., Owen A; Department of Molecular and Clinical Pharmacology, Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K., Nixon GL; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., Leung SC; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K., O'Neill PM; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K. |
| Abstrakt: |
The rapidly growing COVID-19 pandemic is the most serious global health crisis since the "Spanish flu" of 1918. There is currently no proven effective drug treatment or prophylaxis for this coronavirus infection. While developing safe and effective vaccines is one of the key focuses, a number of existing antiviral drugs are being evaluated for their potency and efficiency against SARS-CoV-2 in vitro and in the clinic. Here, we review the significant potential of nitazoxanide (NTZ) as an antiviral agent that can be repurposed as a treatment for COVID-19. Originally, NTZ was developed as an antiparasitic agent especially against Cryptosporidium spp.; it was later shown to possess potent activity against a broad range of both RNA and DNA viruses, including influenza A, hepatitis B and C, and coronaviruses. Recent in vitro assessment of NTZ has confirmed its promising activity against SARS-CoV-2 with an EC 50 of 2.12 μM. Here we examine its drug properties, antiviral activity against different viruses, clinical trials outcomes, and mechanisms of antiviral action from the literature in order to highlight the therapeutic potential for the treatment of COVID-19. Furthermore, in preliminary PK/PD analyses using clinical data reported in the literature, comparison of simulated TIZ (active metabolite of NTZ) exposures at two doses with the in vitro potency of NTZ against SARS-CoV-2 gives further support for drug repurposing with potential in combination chemotherapy approaches. The review concludes with details of second generation thiazolides under development that could lead to improved antiviral therapies for future indications. |
