Cargando…
A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus
Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox....
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477205/ https://www.ncbi.nlm.nih.gov/pubmed/37666979 http://dx.doi.org/10.1038/s41598-023-41820-z |
_version_ | 1785101099617746944 |
---|---|
author | Alandijany, Thamir A. El-Daly, Mai M. Tolah, Ahmed M. Bajrai, Leena H. Khateb, Aiah M. Kumar, Geethu S. Dubey, Amit Dwivedi, Vivek Dhar Azhar, Esam I. |
author_facet | Alandijany, Thamir A. El-Daly, Mai M. Tolah, Ahmed M. Bajrai, Leena H. Khateb, Aiah M. Kumar, Geethu S. Dubey, Amit Dwivedi, Vivek Dhar Azhar, Esam I. |
author_sort | Alandijany, Thamir A. |
collection | PubMed |
description | Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of − 8.88 and − 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of − 10.60 and − 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein–ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection. |
format | Online Article Text |
id | pubmed-10477205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104772052023-09-06 A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus Alandijany, Thamir A. El-Daly, Mai M. Tolah, Ahmed M. Bajrai, Leena H. Khateb, Aiah M. Kumar, Geethu S. Dubey, Amit Dwivedi, Vivek Dhar Azhar, Esam I. Sci Rep Article Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen the problem. Identifying potential drug targets can significantly improve the process of developing potent drug molecules for treating monkeypox. The proteins responsible for viral replication are attractive drug targets. Identifying potential inhibitors from known drug molecules that target these proteins can be key to finding a cure for monkeypox. In this work, two viral proteins, DNA-dependent RNA polymerase (DdRp) and viral core cysteine proteinase, were considered as potential drug targets. Sixteen antibiotic drugs from the tetracycline class were screened against both viral proteins through high-throughput virtual screening. These tetracycline class of antibiotic drugs have the ability to inhibit bacterial protein synthesis, which makes these antibiotics drugs a prominent candidate for drug repurposing. Based on the screening result obtained against DdRp, top two compounds, namely Tigecycline and Eravacycline with docking scores of − 8.88 and − 7.87 kcal/mol, respectively, were selected for further analysis. Omadacycline and minocycline, with docking scores of − 10.60 and − 7.51 kcal/mol, are the top two compounds obtained after screening proteinase with the drug library. These compounds, along with reference compounds GTP for DdRp and tecovirimat for proteinase, were used to form protein–ligand complexes, followed by their evaluation through a 300 ns molecular dynamic simulation. The MM/GBSA binding free energy calculation and principal components analysis of these selected complexes were also conducted for understanding the dynamic stability and binding affinity of these compounds with respective target proteins. Overall, this study demonstrates the repurposing of tetracycline-derived drugs as a therapeutic solution for monkeypox viral infection. Nature Publishing Group UK 2023-09-04 /pmc/articles/PMC10477205/ /pubmed/37666979 http://dx.doi.org/10.1038/s41598-023-41820-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Alandijany, Thamir A. El-Daly, Mai M. Tolah, Ahmed M. Bajrai, Leena H. Khateb, Aiah M. Kumar, Geethu S. Dubey, Amit Dwivedi, Vivek Dhar Azhar, Esam I. A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title | A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title_full | A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title_fullStr | A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title_full_unstemmed | A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title_short | A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
title_sort | multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10477205/ https://www.ncbi.nlm.nih.gov/pubmed/37666979 http://dx.doi.org/10.1038/s41598-023-41820-z |
work_keys_str_mv | AT alandijanythamira amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT eldalymaim amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT tolahahmedm amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT bajraileenah amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT khatebaiahm amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT kumargeethus amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT dubeyamit amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT dwivedivivekdhar amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT azharesami amultitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT alandijanythamira multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT eldalymaim multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT tolahahmedm multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT bajraileenah multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT khatebaiahm multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT kumargeethus multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT dubeyamit multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT dwivedivivekdhar multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus AT azharesami multitargetedcomputationaldrugdiscoveryapproachforrepurposingtetracyclinesagainstmonkeypoxvirus |