Inclusion Complexation of Remdesivir with Cyclodextrins: A Comprehensive Review on Combating Coronavirus Resistance-Current State and Future Perspectives

Abstract

Cyclodextrin (CD) derivatives have gained significant attention in biomedical applications due to their remarkable biocompatibility, unique inclusion capabilities, and potential for functionalization. This review focuses on recent advancements in CD-based assemblies, specifically their role in improving drug delivery, emphasizing remdesivir (RMD). The review introduces CD materials and their versatile applications in self-assembly and supramolecular assembly. CD materials offer immense potential for designing drug delivery systems with enhanced activity. Their inherent inclusion capabilities enable the encapsulation of diverse therapeutic agents, including RMD, resulting in improved solubility, stability, and bioavailability. The recent advances in CD-based assemblies, focusing on their integration with RMD have been concentrated here. Various strategies for constructing these assemblies are discussed, including physical encapsulation, covalent conjugation, and surface functionalization techniques. Furthermore, exploring future directions in these fields has also been provided. Ongoing research efforts are directed toward developing novel CD derivatives with enhanced properties, such as increased encapsulation efficiency and improved release kinetics. Moreover, the integration of CD-based assemblies with advanced technologies such as nanomedicine and gene therapy holds tremendous promise for personalized medicine and precision therapeutics.

Keywords: COVID-19; cyclodextrins; inclusion complexes; remdesivir.

Figure 1

A description of the structure of RMD.

Figure 2

Various types of hosts.

Figure 3

Possible Guest–Host stoichiometric ratio between guest and host (α, β, and γ-CDs) of the ICs [58].

Figure 4

Adverse and toxicological effects of CDs. Reprinted with permission from Ref. [78]. Copyright 2024 Elsevier.

Figure 5

CD inhibited the cytopathic effect (CPE) in lung epithelial cells (MRC−5) and reduction of virus titer (A), and cytopathic effect (CPE) in lung epithelial cell (MRC−5) with OTV and ICs (B). Reprinted with permission from Ref. from [96], Copyright (2024) Elsevier.

Figure 6

Interaction of RMD with CDs (proposed structure).

Figure 7

The uncharged (neutral) and charged (protonated) form of RMD. Reprinted from Ref. [101].

Figure 8

Structures of (A) SBE-β-CD, (B) 5SBE, and (C) 7SBE after 500 ns of MD simulations show the water molecules at less than 3 Å from any atom of the CDs. Carbon is represented by violet, oxygen by red, hydrogen by white, and sulfur by yellow. Sulfur atoms and glucopyranoside rings are represented by spheres, while oxygen and carbon atoms are represented by sticks. Reprinted from Ref. [101].