Tools
Tools
Stachulski, Andrew V., Taujanskas, Joshua, Pate, Sophie L., Rajoli, Rajith K. R., Aljayyoussi, Ghaith, Pennington, Shaun H. 
ORCID: https://orcid.org/0000-0002-7160-6275, Ward, Stephen A. ORCID: https://orcid.org/0000-0003-2331-3192, Hong, Weiqian David, Biagini, Giancarlo A. ORCID: https://orcid.org/0000-0001-6356-6595, Owen, Andrew, Nixon, Gemma L., Leung, Suet C. and O’Neill, Paul M.
(2021)
'Therapeutic Potential of Nitazoxanide: An Appropriate Choice for Repurposing versus SARS-CoV-2?'. ACS Infectious Diseases, Vol 7, Issue 6, pp. 1317-1331.
|
Text
Stachulski et al.pdf - Published Version Download (2MB) | Preview |
Abstract
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 EC50 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.
| Item Type: | Article |
|---|---|
| Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 250 Anti-infective agents (General) QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 253 Anthelmintics WA Public Health > WA 105 Epidemiology WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 505 Viral respiratory tract infections |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.1021/acsinfecdis.0c00478 |
| Depositing User: | Cathy Waldron |
| Date Deposited: | 06 Jan 2021 15:36 |
| Last Modified: | 05 Jul 2021 11:21 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/16581 |
Statistics
Actions (login required)
 |
Edit Item |