The interactions of antiviral drugs and a phosphonium fluorescent dye with proteins as revealed by a multiple ligand simultaneous docking

Abstract

In the present study, the multiple ligands simultaneous docking technique was employed to explore the feasibility of developing the protein-based nanocarriers in which the therapeutic agents (antiviral drugs) will be combined with a visualizing agent (the phosphonium dye TDV). By varying both the protein (serum albumin, lyso-zyme, cytochrome c, insulin) and antiviral agent (favipiravir, molnupiravir, nirmatrelvir, ritonavir) components of the examined complexes it was demonstrated that in the albumin- and cytochrome c-containing systems the TDV and antiviral dyes occupy distinct binding sites on the protein molecule, exhibiting no interference with each other. It was found that the TDV propensity to reside within the same insulin cavity as the antiviral agent might hinder the drug’s release from the nanocarrier. Our results indicate that the most promising energetically stable protein-drug-TDV systems for developing protein-based nanocarriers with the examined antiviral drugs can be created on a basis of serum albumin.