Electrochemical interpretations for the study of molnupiravir binding interactions with bovine serum albumin and DNA and molecular dynamics studies.

Molnupiravir (MPV), an antiviral drug targeting SARS-CoV-2, exerts its effects by inducing lethal mutagenesis in viral RNA. This study investigates MPV's electrochemical behavior and binding interactions with key biomolecules-BSA and ctDNA-via cyclic voltammetry (CV) and molecular dynamics (MD) simulations. The electrochemical behavior of the MPV was studied by using GCE in an across pH levels 4.0, 7.0, and 9.2 phosphate buffer solutions. An irreversible anodic peak was observed at a peak potential of +0.860 V on the GCE at pH 7.0. The electrochemical properties of MPV at the electrode surface, along with the influences of anodic peak potential, peak current, scan rate, and pH, were thoroughly analyzed and discussed. A good linearity in the concentration range of 35 μM-200 μM was shown for MPV. An electro-oxidation mechanism involving a two-electron, two-proton transfer was proposed, supporting an analytical approach for MPV quantification in real samples. In vitro binding studies with ctDNA and BSA by using CV indicates a reduction in peak current and positive potential shift, suggestive of an intercalative or groove-binding interaction mode, corroborated by molecular modeling results that revealed a stable MPV-DNA and MPV-BSA complexes. MD simulations confirmed the stability MPV-DNA and MPV-BSA complexes, stabilized mainly by van der Waals forces with additional contributions from hydrogen bonding and electrostatic interactions. MMGBSA analysis revealed that MPV's affinity for BSA could enhance its pharmacokinetic profile through binding and transport within serum proteins, while DNA interaction, supporting antiviral efficacy, highlights the need for genotoxicity assessment. This integrative study elucidates the electrochemical behavior of MPV and its binding affinity with ctDNA and BSA, correlating these findings with MD simulation results. The results demonstrate a higher binding affinity of MPV with ctDNA and BSA.