A-level – Antivirals Nitazoxanide and RM5038

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Thiazolides are broad-spectrum antiviral drugs and key anti-infective agents, including Nitazoxanide (NTZ) and RM5038. In clinical trials, these compounds helped to protect against RNA and DNA viruses while reducing resistance risks. NTZ is an antiparasitic drug effective against protozoa and parasitic worms, but its active metabolite, tizoxanide, has poor solubility, limiting its effectiveness against respiratory viruses. RM5038 is more active at low micromolar concentrations against viruses like hepatitis B and C.

To address solubility issues, amino acid ester prodrugs were developed. Researchers tested solubility using bulky substituents and HCl salts, but these salts were unstable at pH 5. The degradation products, mainly peptides, showed strong antiviral activity.

For further reading, visit the degree page for Nitazoxanide and RM5038.

A. V. Stachulski, J.-F. Rossignol, S. Pate, J. Taujanskas, J. A. Iggo, R. Aerts, E. Pascal, S. Piacentini, S. La Frazia, M. G. Santoro, L. van Vooren, L. Sintubin, M. Cooper, K. Swift and P. M. O’Neill, ACS Bio & Med Chem Au, 2023, 3, 327-334.