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In the EBOV, two multifunctional proteins, VP35 and VP40, have significant roles in replication, virion assembly, and budding from the cell and have been identified as druggable targets. In this study, we employed in silico methods comprising molecular docking, molecular dynamic simulations, and pharmacological properties to identify prospective drugs for inhibiting VP35 and VP40 proteins from the myxobacterial bioactive natural product repertoire. Cystobactamid 934-2, Cystobactamid 919-1, and Cittilin A bound firmly to VP35. Meanwhile, 2-Hydroxysorangiadenosine, Enhypyrazinone B, and Sorangiadenosine showed strong binding to the matrix protein VP40. Molecular dynamic simulations revealed that, among these compounds, Cystobactamid 919-1 and 2-Hydroxysorangiadenosine had stable interactions with their respective targets. Similarly, molecular mechanics Poisson\u2013Boltzmann surface area (MMPBSA) calculations indicated close-fitting receptor binding with VP35 or VP40. These two compounds also exhibited good pharmacological properties. In conclusion, we identified Cystobactamid 919-1 and 2-Hydroxysorangiadenosine as potential ligands for EBOV that target VP35 and VP40 proteins. These findings signify an essential step in vitro and in vivo to validate their potential for EBOV inhibition.<\/jats:p>","DOI":"10.3390\/biom14060660","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T03:49:28Z","timestamp":1717559368000},"page":"660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Identification of Prospective Ebola Virus VP35 and VP40 Protein Inhibitors from Myxobacterial Natural Products"],"prefix":"10.3390","volume":"14","author":[{"given":"Muhammad","family":"Hayat","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-4142","authenticated-orcid":false,"given":"Muhammad","family":"Rafiq","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Life Sciences and Informatics, Balochistan University of IT, Engineering and Management Sciences, Quetta 87100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhuo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China"},{"name":"Shenzhen Research Institute, Shandong University, Shenzhen 518057, China"},{"name":"Suzhou Research Institute, Shandong University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8336-6638","authenticated-orcid":false,"given":"Yue-Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399404008300","article-title":"Ebola Virus: New Insights into Disease Aetiopathology and Possible Therapeutic Interventions","volume":"6","author":"Geisbert","year":"2004","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJMra1901594","article-title":"Ebola","volume":"382","author":"Feldmann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-020-0147-3","article-title":"Ebola Virus Disease","volume":"6","author":"Jacob","year":"2020","journal-title":"Nat. Rev. Dis. Primer"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"WHO Ebola Response Team, Aylward, B., Barboza, P., Bawo, L., Bertherat, E., Bilivogui, P., Blake, I., Brennan, R., Briand, S., and Chakauya, J.M. (2014). Ebola Virus Disease in West Africa--the First 9 Months of the Epidemic and Forward Projections. N. Engl. J. Med., 371, 1481\u20131495.","DOI":"10.1056\/NEJMoa1411100"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13311-016-0457-z","article-title":"Neurological Complications of Ebola Virus Infection","volume":"13","author":"Billioux","year":"2016","journal-title":"Neurotherapeutics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.paed.2016.11.007","article-title":"Ebola: Lessons Learned","volume":"27","author":"MacDermott","year":"2017","journal-title":"Paediatr. Child Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1038\/s41467-019-12499-6","article-title":"Impacts of Environmental and Socio-Economic Factors on Emergence and Epidemic Potential of Ebola in Africa","volume":"10","author":"Redding","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1073\/pnas.1712263115","article-title":"Ebola Virus Proteins NP, VP35, and VP24 Are Essential and Sufficient to Mediate Nucleocapsid Transport","volume":"115","author":"Takamatsu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/biolog-2017-0012","article-title":"Potential Ebola Drug Targets\u2014Filling the Gap: A Critical Step Forward towards the Design and Discovery of Potential Drugs","volume":"72","author":"Balmith","year":"2017","journal-title":"Biologia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5406","DOI":"10.1128\/JVI.02190-10","article-title":"A New Ebola Virus Nonstructural Glycoprotein Expressed through RNA Editing","volume":"85","author":"Mehedi","year":"2011","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S0966-842X(01)02201-6","article-title":"The Pathogenesis of Ebola Hemorrhagic Fever","volume":"9","author":"Takada","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Olukitibi, T.A., Ao, Z., Mahmoudi, M., Kobinger, G.A., and Yao, X. (2019). Dendritic Cells\/Macrophages-Targeting Feature of Ebola Glycoprotein and Its Potential as Immunological Facilitator for Antiviral Vaccine Approach. Microorganisms, 7.","DOI":"10.3390\/microorganisms7100402"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8756","DOI":"10.1128\/JVI.72.11.8756-8764.1998","article-title":"Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient to Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes","volume":"72","author":"Klenk","year":"1998","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12289","DOI":"10.1073\/pnas.220398297","article-title":"The Ebola Virus VP35 Protein Functions as a Type I IFN Antagonist","volume":"97","author":"Basler","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/08830180213277","article-title":"Viruses and the Type I Interferon Antiviral System: Induction and Evasion","volume":"21","author":"Basler","year":"2002","journal-title":"Int. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Haasnoot, J., de Vries, W., Geutjes, E.-J., Prins, M., de Haan, P., and Berkhout, B. (2007). The Ebola Virus VP35 Protein Is a Suppressor of RNA Silencing. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030086"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.isci.2019.07.003","article-title":"The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus","volume":"19","author":"Jasenosky","year":"2019","journal-title":"iScience"},{"key":"ref_18","first-page":"423","article-title":"The Matrix Protein VP40 from Ebola Virus Octamerizes into Pore-like Structures with Specific RNA Binding Properties","volume":"11","author":"Dessen","year":"2003","journal-title":"Struct. Lond. Engl. 1993"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13871","DOI":"10.1073\/pnas.250277297","article-title":"A PPxY Motif within the VP40 Protein of Ebola Virus Interacts Physically and Functionally with a Ubiquitin Ligase: Implications for Filovirus Budding","volume":"97","author":"Harty","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4855","DOI":"10.1128\/JVI.76.10.4855-4865.2002","article-title":"Ebola Virus VP40 Drives the Formation of Virus-like Filamentous Particles along with GP","volume":"76","author":"Noda","year":"2002","journal-title":"J. Virol."},{"key":"ref_21","unstructured":"Stahelin, R.V. (2014). Membrane Binding and Bending in Ebola VP40 Assembly and Egress. Front. Microbiol., 5."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/viro.2001.0860","article-title":"Vesicular Release of Ebola Virus Matrix Protein VP40","volume":"283","author":"Timmins","year":"2001","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.1093\/emboj\/19.16.4228","article-title":"Crystal Structure of the Matrix Protein VP40 from Ebola Virus","volume":"19","author":"Dessen","year":"2000","journal-title":"EMBO J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1074\/jbc.M112.443960","article-title":"The Ebola Virus Matrix Protein Penetrates into the Plasma Membrane: A Key Step in Viral Protein 40 (VP40) Oligomerization and Viral Egress","volume":"288","author":"Soni","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11452","DOI":"10.1128\/JVI.00853-07","article-title":"Role for Amino Acids 212KLR214 of Ebola Virus VP40 in Assembly and Budding","volume":"81","author":"McCarthy","year":"2007","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1128\/JVI.01160-10","article-title":"Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway","volume":"85","author":"Fabozzi","year":"2011","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lee, J.-Y., Kuo, C.-J., Shin, J.S., Jung, E., Liang, P.-H., and Jung, Y.-S. (2021). Identification of Non-Covalent 3C-like Protease Inhibitors against Severe Acute Respiratory Syndrome Coronavirus-2 via Virtual Screening of a Korean Compound Library. Bioorg. Med. Chem. Lett., 42.","DOI":"10.1016\/j.bmcl.2021.128067"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/13543784.2021.1881061","article-title":"Targeting Ebola Virus Replication through Pharmaceutical Intervention","volume":"30","author":"Hansen","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s40265-020-01452-3","article-title":"REGN-EB3: First Approval","volume":"81","author":"Markham","year":"2021","journal-title":"Drugs"},{"key":"ref_30","first-page":"483","article-title":"Atoltivimab\/Maftivimab\/Odesivimab (Inmazeb) Combination to Treat Infection Caused by Zaire Ebolavirus","volume":"57","author":"Saxena","year":"2021","journal-title":"Drugs Today Barc. Spain 1998"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1007\/s11095-019-2629-0","article-title":"The Natural Product Eugenol Is an Inhibitor of the Ebola Virus In Vitro","volume":"36","author":"Lane","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/sj.jim.7000025","article-title":"Myxobacteria, Producers of Novel Bioactive Substances","volume":"27","author":"Reichenbach","year":"2001","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jbiotec.2003.07.015","article-title":"Myxobacteria: Proficient Producers of Novel Natural Products with Various Biological Activities--Past and Future Biotechnological Aspects with the Focus on the Genus Sorangium","volume":"106","author":"Gerth","year":"2003","journal-title":"J. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1099\/ijsem.0.002569","article-title":"Nannocystis Konarekensis Sp. Nov., a Novel Myxobacterium from an Iranian Desert","volume":"68","author":"Mohr","year":"2018","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1039\/C6NP00106H","article-title":"Natural Products from Myxobacteria: Novel Metabolites and Bioactivities","volume":"34","author":"Herrmann","year":"2017","journal-title":"Nat. Prod. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1039\/c001260m","article-title":"Myxobacterial Secondary Metabolites: Bioactivities and Modes-of-Action","volume":"27","author":"Weissman","year":"2010","journal-title":"Nat. Prod. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1039\/b817073h","article-title":"The Impact of Genomics on the Exploitation of the Myxobacterial Secondary Metabolome","volume":"26","author":"Wenzel","year":"2009","journal-title":"Nat. Prod. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12760","DOI":"10.1002\/anie.201705913","article-title":"Discovery and Total Synthesis of Natural Cystobactamid Derivatives with Superior Activity against Gram-Negative Pathogens","volume":"56","author":"Testolin","year":"2017","journal-title":"Angew. Chem. Int. Ed Engl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.jhep.2015.06.002","article-title":"Soraphen A: A Broad-Spectrum Antiviral Natural Product with Potent Anti-Hepatitis C Virus Activity","volume":"63","author":"Koutsoudakis","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.antiviral.2016.05.017","article-title":"Identification of Entry Inhibitors of Ebola Virus Pseudotyped Vectors from a Myxobacterial Compound Library","volume":"132","author":"Beck","year":"2016","journal-title":"Antiviral Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D437","DOI":"10.1093\/nar\/gkaa1038","article-title":"RCSB Protein Data Bank: Powerful New Tools for Exploring 3D Structures of Biological Macromolecules for Basic and Applied Research and Education in Fundamental Biology, Biomedicine, Biotechnology, Bioengineering and Energy Sciences","volume":"49","author":"Burley","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_42","first-page":"D271","article-title":"The RCSB Protein Data Bank: Integrative View of Protein, Gene and 3D Structural Information","volume":"45","author":"Rose","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: A Unified Platform for Automated Protein Structure and Function Prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"W174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER Server: New Development for Protein Structure and Function Predictions","volume":"43","author":"Yang","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, Y. (2008). I-TASSER Server for Protein 3D Structure Prediction. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-40"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology Modelling of Protein Structures and Complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1093\/nar\/gkg565","article-title":"VADAR: A Web Server for Quantitative Evaluation of Protein Structure Quality","volume":"31","author":"Willard","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New Data Content and Improved Web Interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1021\/ja0410237","article-title":"ChemDraw Ultra 9.0. CambridgeSoft, 100 CambridgePark Drive, Cambridge, MA 02140. Www. Cambridgesoft.Com. See Web Site for Pricing Options","volume":"127","author":"Cousins","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminformatics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gky473","article-title":"CASTp 3.0: Computed Atlas of Surface Topography of Proteins","volume":"46","author":"Tian","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, D.E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the ACM\/IEEE SC 2006 Conference (SC\u201906), Tampa, FL, USA.","DOI":"10.1109\/SC.2006.54"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/jcc.20267","article-title":"A Fast, Scalable Method for the Parallel Evaluation of Distance-Limited Pairwise Particle Interactions","volume":"26","author":"Shaw","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical Dynamics: Equilibrium Phase-Space Distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys. Rev. Gen. Phys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant Pressure Molecular Dynamics Algorithms","volume":"101","author":"Martyna","year":"1994","journal-title":"J. Chem. Phys."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1110\/ps.04774004","article-title":"In Silico Protein Design by Combinatorial Assembly of Protein Building Blocks","volume":"13","author":"Tsai","year":"2009","journal-title":"Protein Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera? A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Nasution, M.A.F., Alkaff, A.H., and Tambunan, U.S.F. (2018). Discovery of Indonesian Natural Products as Potential Inhibitor of Ebola Virus VP40 through Molecular Docking Simulation, AIP. Conference Proceedings.","DOI":"10.1063\/1.5064052"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-1-4939-6634-9_5","article-title":"Computer-Aided Drug Design Methods","volume":"1520","author":"Yu","year":"2017","journal-title":"Methods Mol. Biol. Clifton NJ"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular Docking and Structure-Based Drug Design Strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Molecules"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tibs.2019.06.004","article-title":"Bringing Molecular Dynamics Simulation Data into View","volume":"44","author":"Hildebrand","year":"2019","journal-title":"Trends Biochem. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Rasheed, M.A., Iqbal, M.N., Saddick, S., Ali, I., Khan, F.S., Kanwal, S., Ahmed, D., Ibrahim, M., Afzal, U., and Awais, M. (2021). Identification of Lead Compounds against Scm (Fms10) in Enterococcus Faecium Using Computer Aided Drug Designing. Life, 11.","DOI":"10.3390\/life11020077"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wilson, A.G.E. (2015). New Horizons in Predictive Drug Metabolism and Pharmacokinetics, The Royal Society of Chemistry.","DOI":"10.1039\/9781782622376"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"G_mmpbsa \u2014A GROMACS Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.2174\/1570180820666230224112505","article-title":"Description and In Silico ADME Studies of US-FDA Approved Drugs orDrugs under Clinical Trial Which Violate the Lipinski\u2019s Rule of 5","volume":"21","author":"Lohit","year":"2024","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1039\/C9SC04769G","article-title":"Synthetic Studies of Cystobactamids as Antibiotics and Bacterial Imaging Carriers Lead to Compounds with High in Vivo Efficacy","volume":"11","author":"Testolin","year":"2020","journal-title":"Chem. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.puhe.2016.10.020","article-title":"The Health Impact of the 2014-15 Ebola Outbreak","volume":"143","author":"Elston","year":"2017","journal-title":"Public Health"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Broni, E., Ashley, C., Adams, J., Manu, H., Aikins, E., Okom, M., Miller, W.A., Wilson, M.D., and Kwofie, S.K. (2023). Cheminformatics-Based Study Identifies Potential Ebola VP40 Inhibitors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076298"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mirza, M., and Ikram, N. (2016). Integrated Computational Approach for Virtual Hit Identification against Ebola Viral Proteins VP35 and VP40. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111748"},{"key":"ref_75","first-page":"555","article-title":"In Silico Study of Plant Polyphenols\u2019 Interactions with VP24\u2013Ebola Virus Matrix Protein","volume":"62","year":"2015","journal-title":"Acta Chim. Slov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s12539-015-0109-8","article-title":"Flavonoids as Multi-Target Inhibitors for Proteins Associated with Ebola Virus: In Silico Discovery Using Virtual Screening and Molecular Docking Studies","volume":"8","author":"Raj","year":"2016","journal-title":"Interdiscip. Sci. Comput. Life Sci."},{"key":"ref_77","first-page":"489","article-title":"Comparative insillico studies on phytochemicals of ocimum as natural inhibitors of ebola vp-35 protein","volume":"10","author":"Kashyap","year":"2019","journal-title":"Indo Am. J. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"277","DOI":"10.12688\/f1000research.5741.1","article-title":"A Common Feature Pharmacophore for FDA-Approved Drugs Inhibiting the Ebola Virus","volume":"3","author":"Ekins","year":"2014","journal-title":"F1000Research"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.celrep.2015.03.034","article-title":"An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions","volume":"11","author":"Leung","year":"2015","journal-title":"Cell Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5837","DOI":"10.1093\/nar\/gkz340","article-title":"Ebola Virus VP35 Has Novel NTPase and Helicase-like Activities","volume":"47","author":"Shu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1021\/acs.jproteome.0c00473","article-title":"Ebola Virus VP35 Protein: Modeling of the Tetrameric Structure and an Analysis of Its Interaction with Human PKR","volume":"19","author":"Banerjee","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/j.jmb.2014.01.010","article-title":"In Silico Derived Small Molecules Bind the Filovirus VP35 Protein and Inhibit Its Polymerase Cofactor Activity","volume":"426","author":"Brown","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Dilley, K.A., Voorhies, A.A., Luthra, P., Puri, V., Stockwell, T.B., Lorenzi, H., Basler, C.F., and Shabman, R.S. (2017). The Ebola Virus VP35 Protein Binds Viral Immunostimulatory and Host RNAs Identified through Deep Sequencing. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178717"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"10581","DOI":"10.1128\/JVI.00925-10","article-title":"Basic Residues within the Ebolavirus VP35 Protein Are Required for Its Viral Polymerase Cofactor Function","volume":"84","author":"Prins","year":"2010","journal-title":"J. Virol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1073\/pnas.0910547107","article-title":"Ebolavirus VP35 Uses a Bimodal Strategy to Bind dsRNA for Innate Immune Suppression","volume":"107","author":"Kimberlin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1073\/pnas.0807854106","article-title":"Structure of the Ebola VP35 Interferon Inhibitory Domain","volume":"106","author":"Leung","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/nsmb.1765","article-title":"Structural Basis for dsRNA Recognition and Interferon Antagonism by Ebola VP35","volume":"17","author":"Leung","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Darko, L.K.S., Broni, E., Amuzu, D.S.Y., Wilson, M.D., Parry, C.S., and Kwofie, S.K. (2021). Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121796"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.1016\/j.bmc.2016.08.065","article-title":"In Silico and in Vitro Methods to Identify Ebola Virus VP35-dsRNA Inhibitors","volume":"24","author":"Glanzer","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"105251","DOI":"10.1016\/j.antiviral.2022.105251","article-title":"Cynarin Blocks Ebola Virus Replication by Counteracting VP35 Inhibition of Interferon-Beta Production","volume":"198","author":"Corona","year":"2022","journal-title":"Antiviral Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6367","DOI":"10.1021\/acs.biochem.8b00892","article-title":"Identification of Myricetin as an Ebola Virus VP35\u2013Double-Stranded RNA Interaction Inhibitor through a Novel Fluorescence-Based Assay","volume":"57","author":"Daino","year":"2018","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0168-1702(95)00080-1","article-title":"Differentiation of Filoviruses by Electron Microscopy","volume":"39","author":"Geisbert","year":"1995","journal-title":"Virus Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1128\/JVI.79.3.1898-1905.2005","article-title":"VP40 Octamers Are Essential for Ebola Virus Replication","volume":"79","author":"Hoenen","year":"2005","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"8596","DOI":"10.1074\/jbc.AC120.013171","article-title":"Angiomotin Regulates Budding and Spread of Ebola Virus","volume":"295","author":"Han","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/JVI.77.3.1812-1819.2003","article-title":"Overlapping Motifs (PTAP and PPEY) within the Ebola Virus VP40 Protein Function Independently as Late Budding Domains: Involvement of Host Proteins TSG101 and VPS-4","volume":"77","author":"Licata","year":"2003","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.cell.2013.07.015","article-title":"Structural Rearrangement of Ebola Virus VP40 Begets Multiple Functions in the Virus Life Cycle","volume":"154","author":"Bornholdt","year":"2013","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.3390\/v6103837","article-title":"A Loop Region in the N-Terminal Domain of Ebola Virus VP40 Is Important in Viral Assembly, Budding, and Egress","volume":"6","author":"Soni","year":"2014","journal-title":"Viruses"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7294","DOI":"10.1128\/JVI.00591-14","article-title":"Small-Molecule Probes Targeting the Viral PPxY-Host Nedd4 Interface Block Egress of a Broad Range of RNA Viruses","volume":"88","author":"Han","year":"2014","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"15076","DOI":"10.1038\/s41598-019-50701-3","article-title":"Binding Site Plasticity in Viral PPxY Late Domain Recognition by the Third WW Domain of Human NEDD4","volume":"9","author":"Palencia","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Johnson, K., Pokhrel, R., Budicini, M., Gerstman, B., Chapagain, P., and Stahelin, R. (2020). A Conserved Tryptophan in the Ebola Virus Matrix Protein C-Terminal Domain Is Required for Efficient Virus-Like Particle Formation. Pathogens, 9.","DOI":"10.3390\/pathogens9050402"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:53:50Z","timestamp":1760108030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/6\/660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":100,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["biom14060660"],"URL":"https:\/\/doi.org\/10.3390\/biom14060660","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]}}}