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 μ M in the linear range of 10–200 μ M, 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 × 10 4 M. As for molecular docking techniques, the binding energy of MLP with DNA is −8.1 kcal mol −1 , 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. This electrochemical study examined Molnupiravir’s (MLP) interaction with calf thymus double-stranded DNA (ct-dsDNA) for the first time. In a solution with both, the biosensor surface investigated the interaction of ct-dsDNA immobilized on the GCE surface and the bare GCE examined the interaction of MLP-ct-dsDNA. Differential pulse voltammetry shows that MLP-dAdo binding mode decreases oxidation signals after incubation with various doses. The binding constant of MLP and ct-dsDNA was calculated using cyclic voltammetry. A molecular docking simulation contributed electrochemical interaction study.