Simultaneous Docking of Antiviral Drugs and Cyanine Dyes with Proteins Using Multiple Ligand Approach

Abstract

The protein-based nanosystems for targeted drug delivery of a wide array of substances, ranging from small drugs and therapeutic proteins to nucleic acids and genes, attract increasing attention due to their biocompatibility and biodegradability, extraordinary binding capacity for different ligands, accessibility from natural sources, effective drug protection and gentle encapsulation conditions. Due to the multitude of binding pockets and functional groups on the protein surface, these nanocarriers seem to be highly efficient multifunctional nanotheranostic systems that could incorporate both a therapeutic drug and a visualizing agent. This integration serves multiple purposes, including the regulation of drug release, monitoring the alterations at the target site in response to treatment, and offering crucial insights into the efficacy of the intervention in its early stages. The development of these advanced nanosystems necessitates a thorough comprehension of the potential interactions within these intricate systems. In the present study we assessed the potential of six trimethine and seven pentamethine cyanine dyes to serve as visualizing agents in the drug-protein-dye systems which include functionally significant proteins (cytochrome c, serum albumin, lysozyme and insulin and four antiviral drugs, viz. favipiravir, molnupiravir, nirmatrelvir and ritonavir. The ternary systems with the highest dye-protein surface shape complementarity were established for all groups of the examined cyanine dyes. The influence of the cyanine dye structure on the stability of the drug-protein-dye complexes was assessed. The obtained results indicate that the dye-protein affinity is not solely dependent on the length of the polymethine chain. It was found that the most prospective drug delivery systems containing the trimethines and pentamethines as visualizing agents are AK5-6-, AK5-8- and AK3-11-drug-albumin complexes.

Keywords

• Protein-drug-dye complexes
• Antiviral agents
• Protein nanoparticles
• Drug nanocarriers
• Cyanine dyes
• Multiple molecular docking