Improving the solubility of remdesivir–cyclodextrin encapsulations in water-saturated 1-octanol solution: A molecular dynamics simulation study

Remdesivir was selected as a treatment for viral infections due to its efficacy as an antiviral agent against various RNA viruses such as Ebola and coronaviruses. The drug exerts its benefits during the later stages of viral infection, particularly post-fusion, endocytosis, translation, and proteolysis within host cells. It integrates into emerging viral RNA chains, disrupting transcription and ultimately inhibiting replication. However, its low water solubility poses limitations for clinical development. To enhance its solubility, current efforts focus on creating drug inclusion complexes using cyclodextrin derivatives. In this study, in silico techniques, including molecular docking and molecular dynamics simulations, were employed to investigate the molecular mechanisms and stability of remdesivir encapsulation using cyclodextrin derivatives. Various cyclodextrins were utilized, including beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin (HPBCD), and sulfobutylether-beta-cyclodextrin (SBCD), docked against remdesivir. Molecular dynamics simulations were conducted in a water-saturated 1-octanol environment, a biphasic solvent system frequently used to mimic biological membrane conditions and assess solubility and partitioning behavior. Molecular docking results indicated that the complexes of remdesivir with HPBCD and SBCD exhibited the lowest binding energies of −10.69 kcal/mol and −8.34 kcal/mol, respectively. Furthermore, molecular dynamics simulations over 100 ns showed that these complexes maintained good stability. Analysis of molecular motion, RMSD, RDF, Rg, and SASA revealed increased water solubility and stability of the complexes. This evidence suggests that encapsulating remdesivir with HPBCD and SBCD can enhance its solubility.