Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study

Abstract

The World Health Organization declared monkeypox a global public health emergency on 23 July 2022. This disease was caused by the monkeypox virus (MPXV), which was first identified in 1958 in Denmark. The MPXV is a member of the Poxviridae family, the Chordopoxvirinae subfamily, and the genus Orthopoxvirus, which share high similarities with the vaccinia virus (the virus used to produce the smallpox vaccine). For the initial stage of infection, the MPXV needs to attach to the human cell surface glycosaminoglycan (GAG) adhesion molecules using its E8 protein. However, up until now, neither a structure for the MPXV E8 protein nor a specific cure for the MPXV exists. This study aimed to search for small molecules that inhibit the MPXV E8 protein, using computational approaches. In this study, a high-quality three-dimensional structure of the MPXV E8 protein was retrieved by homology modeling using the AlphaFold deep learning server. Subsequent molecular docking and molecular dynamics simulations (MDs) for a cumulative duration of 2.1 microseconds revealed that ZINC003977803 (Diosmin) and ZINC008215434 (Flavin adenine dinucleotide-FAD) could be potential inhibitors against the E8 protein with the MM/GBSA binding free energies of −38.19 ± 9.69 and −35.59 ± 7.65 kcal·mol−1, respectively.

Structure-based design of promising natural products to inhibit thymidylate kinase from Monkeypox virus and validation using free energy calculations

“…Similarly by combining high-throughput computational molecular screening and experimental methods also reported promising drugs that target A27 protein from MPXV. The models from these studies can be used to experimentally validate our hits and may be taken for further clinical consideration [ 70 ]. The structural dynamic features of our hits further demonstrated the robust pharmacological potential of our compounds in inhibiting the replication of MPXV.…”

Emergence of monkeypox: a worldwide public health crisis

“…In this study, homology modeling with the AlphaFold deep learning server was implemented to obtain a high-quality 3D structure of the MPV E8 protein. Diosmin and FAD (flavin adenine dinucleotide) were reported to have potential as hit compounds against the MPV E8 protein, which might aid in restricting viral entrance and suppress the virus in subsequent fusion events [ 106 ].…”

Flavonoids as dual-target inhibitors against α-glucosidase and α-amylase: a systematic review of in vitro studies

“…In most cases, this three-carbon system forms a heterocyclic pyran ring (C ring). These compounds are well-known for their diverse health-promoting properties, including anti-inflammatory [ 11 ], anti-oxidative [ 12 ], anti-infective [ 13 ], and anti-obesity effects [ 14 ]. Notably, several studies have highlighted the potential of flavonoids as anti-diabetic agents due to their strong inhibition of α-glucosidase and moderate inhibition of α-amylase, making them promising candidates for the development of anti-diabetic drugs with minimal gastrointestinal side effects [ 15 – 17 ].…”