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

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 Orthop...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570275/
https://www.ncbi.nlm.nih.gov/pubmed/36232872
http://dx.doi.org/10.3390/ijms231911570
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author 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
author_facet 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
author_sort Lam, Thua-Phong
collection PubMed
description 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.
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spelling pubmed-95702752022-10-17 Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study 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 Int J Mol Sci Article 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. MDPI 2022-09-30 /pmc/articles/PMC9570275/ /pubmed/36232872 http://dx.doi.org/10.3390/ijms231911570 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title_full Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title_fullStr Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title_full_unstemmed Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title_short Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study
title_sort identification of diosmin and flavin adenine dinucleotide as repurposing treatments for monkeypox virus: a computational study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570275/
https://www.ncbi.nlm.nih.gov/pubmed/36232872
http://dx.doi.org/10.3390/ijms231911570
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