Computational Repurposing of Mitoxantrone-Related Structures against Monkeypox Virus: A Molecular Docking and 3D Pharmacophore Study

Abstract

Monkeypox is caused by a DNA virus known as the monkeypox virus (MPXV) belonging to the Orthopoxvirus genus of the Poxviridae family. Monkeypox is a zoonotic disease where the primary significant hosts are rodents and non-human primates. There is an increasing global incidence with a 2022 outbreak that has spread to Europe in the middle of the COVID-19 pandemic. The new outbreak has novel, previously undiscovered mutations and variants. Currently, the US Food and Drug Administration (FDA) approved poxvirus treatment involving the use of tecovirimat. However, there has otherwise been limited research interest in monkeypox. Mitoxantrone (MXN), an anthracycline derivative, an FDA-approved therapeutic for treating cancer and multiple sclerosis, was previously reported to exhibit antiviral activity against the vaccinia virus and monkeypox virus. In this study, virtual screening, molecular docking analysis, and pharmacophore ligand-based modelling were employed on anthracene structures (1-13) closely related to MXN to explore the potential repurposing of multiple compounds from the PubChem library. Four chemical structures (2), (7), (10) and (12) show a predicted high binding potential to suppress viral replication.