Electrochemical Investigations and Molecular Docking Analysis to Evaluate the Molnupiravir-Calf Thymus dsDNA Interaction

Abstract Molnupiravir (MLP) is an important antiviral drug recommended for the treatment of COVID-19. In order to design new pharmaceuticals, exploring drug and DNA interaction is crucial . This study aimed to determine the interaction of MLP with calf thymus double-stranded DNA (ct-dsDNA) by electrochemical methods. Investigation of these interactions was carried out using the differential pulse voltammetry technique (DPV) on the biosensor surface and in-solution studies. Changes in ct-dsDNA between deoxyguanosine (dGuo) and deoxyadenosine (dAdo) oxidation signals were examined before and after the interaction. It was found that MLP interacts significantly with bases of ct-dsDNA dAdo. Limits of detection and quantification for MLP-ct-dsDNA interaction were calculated as 2.93 and 9.67 µM in the linear range of 10-200 µM, respectively, based on dAdo's decreasing peak current. To calculate the binding constant of MLP and ct-dsDNA, cyclic voltammetry was used, and it was found to be 8.6×104 M. As for molecular docking techniques, the binding energy of MLP with DNA is −8.1 kcal/mol, and this binding occurred by a combination of strong conventional hydrogen bonding to both adenine and guanine base pair edges, which indicates the interaction of MLP with DNA.