Interaction of zanamivir with DNA and RNA: Models for drug–DNA and drug–RNA bindings

Zanamivir (ZAN) is the first of a new generation of influenza virus-specific drugs known as neuraminidase inhibitors, which acts by interfering with life cycles of influenza viruses A and B. It prevents the virus spreading infection to other cells by blocking the neuraminidase enzyme present on the surface of the virus. The aim of this study was to examine the stability and structural features of calf thymus DNA and yeast RNA complexes with zanamivir in aqueous solution, using constant DNA or RNA concentration (12.5 mM) and various zanamivir/polynucleotide (P) ratios of 1/20, 1/10, 1/4, and 1/2. FTIR and UV–visible spectroscopy are used to determine the drug external binding modes, the binding constant and the stability of zanamivir–DNA and RNA complexes in aqueous solution. Structural analysis showed major interaction of zanamivir with G-C (major groove) and A-T (minor groove) base pairs and minor perturbations of the backbone PO₂ group with overall binding constants of K_{zanamivir–DNA} = 1.30 × 10⁴ M⁻¹ and K_{zanamivir–RNA} = 1.38 × 10⁴ M⁻¹. The drug interaction induces a partial B to A-DNA transition, while RNA remains in A-conformation.