Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola
Abstract Background Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a sing...
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | BMC Bioinformatics |
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| Online Access: | http://link.springer.com/article/10.1186/s12859-018-2387-8 |
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| author | Mochammad Arfin Fardiansyah Nasution Erwin Prasetya Toepak Ahmad Husein Alkaff Usman Sumo Friend Tambunan |
| author_facet | Mochammad Arfin Fardiansyah Nasution Erwin Prasetya Toepak Ahmad Husein Alkaff Usman Sumo Friend Tambunan |
| author_sort | Mochammad Arfin Fardiansyah Nasution |
| collection | DOAJ |
| description | Abstract Background Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle. Therefore, the development of a new Ebola treatment can be targeted towards EBOV NP. Results In this work, we screened about 190,084 natural product compounds from ZINC15 database through in silico virtual screening and flexible docking simulation. Furthermore, the bioavailability and toxicity prediction have been conducted as well. Two best ligands according to the simulation and prediction tests were progressed into the molecular dynamics simulation. Conclusion In the end, we found that our proposed ligands, namely α-lipomycin (ZINC56874155) and 3-(((S)-1-amino-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)-5-((5-((5R,7S)-5,7-dihydroxy-3-oxodecyl)-2-hydroxyphenoxy) methyl)pyrrolo[3,4-b]pyrrol-5-ium (ZINC85628951), showed the promising results to be developed as a lead compounds for treating Ebola. Therefore, an experimental study is required to validate their inhibition activities against EBOV NP. |
| first_indexed | 2024-12-12T18:27:32Z |
| format | Article |
| id | doaj.art-16988c4fef174394a81abae37b46967c |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-12T18:27:32Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-16988c4fef174394a81abae37b46967c2022-12-22T00:15:59ZengBMCBMC Bioinformatics1471-21052018-11-0119S1413714910.1186/s12859-018-2387-8Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating EbolaMochammad Arfin Fardiansyah Nasution0Erwin Prasetya Toepak1Ahmad Husein Alkaff2Usman Sumo Friend Tambunan3Bioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas IndonesiaBioinformatics Research Group, Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas IndonesiaAbstract Background Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle. Therefore, the development of a new Ebola treatment can be targeted towards EBOV NP. Results In this work, we screened about 190,084 natural product compounds from ZINC15 database through in silico virtual screening and flexible docking simulation. Furthermore, the bioavailability and toxicity prediction have been conducted as well. Two best ligands according to the simulation and prediction tests were progressed into the molecular dynamics simulation. Conclusion In the end, we found that our proposed ligands, namely α-lipomycin (ZINC56874155) and 3-(((S)-1-amino-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)-5-((5-((5R,7S)-5,7-dihydroxy-3-oxodecyl)-2-hydroxyphenoxy) methyl)pyrrolo[3,4-b]pyrrol-5-ium (ZINC85628951), showed the promising results to be developed as a lead compounds for treating Ebola. Therefore, an experimental study is required to validate their inhibition activities against EBOV NP.http://link.springer.com/article/10.1186/s12859-018-2387-8Ebola virusEbola virus nucleocapsidNatural product compoundsVirtual screeningFlexible dockingMolecular dynamics simulation |
| spellingShingle | Mochammad Arfin Fardiansyah Nasution Erwin Prasetya Toepak Ahmad Husein Alkaff Usman Sumo Friend Tambunan Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola BMC Bioinformatics Ebola virus Ebola virus nucleocapsid Natural product compounds Virtual screening Flexible docking Molecular dynamics simulation |
| title | Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola |
| title_full | Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola |
| title_fullStr | Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola |
| title_full_unstemmed | Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola |
| title_short | Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola |
| title_sort | flexible docking based molecular dynamics simulation of natural product compounds and ebola virus nucleocapsid ebov np a computational approach to discover new drug for combating ebola |
| topic | Ebola virus Ebola virus nucleocapsid Natural product compounds Virtual screening Flexible docking Molecular dynamics simulation |
| url | http://link.springer.com/article/10.1186/s12859-018-2387-8 |
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