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

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11570
• Main Authors: Lam, Thua-Phong, Tran, Viet-Hung, Mai, Tan Thanh, Lai, Nghia Vo-Trong, Dang, Bao-Tran Ngoc, Le, Minh-Tri, Tran, Thanh-Dao, Trinh, Dieu-Thuong Thi, Thai, Khac-Minh
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-09-2022; MDPI
• Subjects: Adenine; Binding sites; Cell adhesion molecules; Cell surface; Chondroitin sulfate; Computer applications; Coronaviruses; COVID-19; Deep learning; Diosmin; Disease transmission; dynamics simulation; E8 protein; Flavin; Flavin-Adenine Dinucleotide; Gag protein; Glycosaminoglycans; Heparan sulfate; Homology; homology modeling; Humans; Infections; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Monkeypox; Monkeypox virus; Mpox (monkeypox) - prevention & control; Proteins; Public health; R&D; repurposing treatment; Research & development; Smallpox; Smallpox Vaccine; Viral Proteins; Viruses; homology modeling; molecular docking; MM/GBSA; repurposing treatment; E8 protein; dynamics simulation; monkeypox virus
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911570

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
, respectively.