Exploring doxycycline–gamma cyclodextrin inclusion complexes: preparation, characterization and molecular docking with monkeypox virus

Abstract

Monkeypox virus (MPXV), a zoonotic virus similar to smallpox in some aspects, poses a significant public health threat due to its high mortality and morbidity rates. Historically confined to Africa, recent outbreaks have resulted in global spread, with no currently available antiviral treatment for MPXV infections. This study aims to address this gap by employing computational and experimental methods to identify potential therapeutic candidates. Molecular docking and molecular dynamics simulations were utilized to repurpose doxycycline hyclate (DOXY), an antiviral drug known for its high efficacy and resistance barrier. To enhance DOXY's solubility and stability, its inclusion complex (IC) with γ-cyclodextrin (γ-CD) was synthesized and characterized using ultraviolet-visible (UV-visible) spectroscopy, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR) analyses, which confirmed the formation of the complex. Computational studies further evaluated DOXY's potential as an MPXV inhibitor, complemented by molecular dynamic simulations and density functional theory (DFT) calculations. The results demonstrated that DOXY, encapsulated within γ-CD, exhibits promising inhibitory potential against MPXV. These findings suggest that DOXY could serve as an effective lead compound for developing antiviral treatments, offering a time-efficient and cost-effective approach to addressing the global monkeypox outbreak.