Work

Theoretical, biological, and electrochemical explanation of the complexity of Peramivir’s drug–DNA interaction

Year: 2025

Type: article

Abstract: In this study, an in-depth investigation was carried out on the interaction between the anti-influenza drug peramivir (PMV) and various DNA, including double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), polyadenylic acid (PolyA), polyguanylic acid (PolyG) and plasmid pUC19, employing square-wave voltammetry (SWV), spectrophotometry, plasmid relaxation assays, and density functional theory (DFT). Voltammetric measurements demonstrated that peramivir significantly influences the unwinding of the DNA double helix. The data also suggest that PMV binds within the DNA groove and interacts with nucleobases, showing a stronger affinity toward guanine. These findings were confirmed by the results of DFT calculations, which additionally demonstrated the importance of PMV-nucleobase hydrogen bond formation and interactions of this drug with the sugar-phosphate backbones of DNA for the stabilization of DNA:PMV complexes. Complementarily plasmid relaxation assays indicate that PMV does not cause significant DNA damage such as single- or double-strand breaks, but also does not provide any protection against oxidative DNA damage. These findings imply that the drug's mechanism of action is centred more on molecular interaction with DNA rather than on compromising its structural integrity.

Source: Scientific Reports

DOI: 10.1038/s41598-025-28369-9

Authors: Monika Wypych, Anna Ignaczak, Paulina Tokarz, Jagoda Seroka, Kamila Koszelska, Sylwia Smarzewska

Institutions: University of Łódź, Polish Academy of Sciences

Language: English

Topic: DNA and Nucleic Acid Chemistry

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690