Fullerene Derivatives for Drug Delivery against COVID-19: A Molecular Dynamics Investigation of Dendro[60]fullerene as Nanocarrier of Molnupiravir

Abstract

In this paper, a theoretical investigation is made regarding the possibility of using a water-soluble derivative of C₆₀ as a drug delivery agent for treating Coronavirus disease 2019 (COVID-19). Molnupiravir is chosen as the transporting pharmaceutical compound since it has already proved to be very helpful in saving lives in case of hospitalization. According to the proposed formulation, a carboxyfullerene known as dendro[60]fullerene is externally connected with two molnupiravir molecules. Two properly formed nitrogen single bonds (N-N) are used as linkers between the dendro[60]fullerene and the two molnupiravir molecules to create the final form of the C₆₀ derivate/molnupiravir conjugate. The energetics of the developed molecular system and its interaction with water and n-octanol are extensively studied via classical molecular dynamics (MD) using the COMPASS II force field. To study the interactions with water and n-octanol, an appropriate periodic amorphous unit cell is created that contains a single C₆₀ derivative/molnupiravir system surrounded by numerous solvent molecules and simulated via MD in room conditions. In addition, the corresponding solvation-free energies of the investigated drug delivery system are computed and set in contrast with the corresponding properties of the water-soluble dendro[60]fullerene, to test its solubility capabilities.

Keywords: COVID-19; drug delivery; fullerene; molecular dynamics; molnupiravir; solvation free energy.

Figure 1

The chemical structure of the water-soluble dendro[60]fullerene.

Figure 2

The proposed drug delivery system: (a) Locations of molnupiravir molecules input in dendro[60]fullerene and (b) final chemical structure.

Figure 3

The optimized molecular structure of the dendro[60]fullerene.

Figure 4

The optimized molecular structure of the molnupiravir.

Figure 5

The optimized molecular structure of the dendro[60]fullerene with two molnupiravir molecules attached in the opposing dendrimer building blocks.

Figure 6

The utilized solvent particles after being optimized: (a) Water and (b) n-octanol (1-octanol).

Figure 7

The unit cell for simulating the dendro[60]fullerene as a solute: (a) Solute central position, (b) solute Connolly surface, (c) solute in water solvent, and (d) solute in n-octanol solvent.

Figure 8

The unit cell for simulating the dendro[60]fullerene/molnupiravir drug delivery system as a solute: (a) Solute central position, (b) solute Connolly surface, (c) solute in water solvent, and (d) solute in n-octanol solvent.

Figure 9

The density of the four investigated unit cells versus time during the NPT MD analysis.

Figure 10

The free energies of the dendro[60]fullerene/molnupiravir drug delivery system and the dendro[60]fullerene in water versus the value of the coupling coefficient.

Figure 11

The free energies of the dendro[60]fullerene/molnupiravir drug delivery system and the dendro[60]fullerene in n-octanol versus the value of the coupling coefficient.