Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics
Nipah virus (NiV) is a recently emerged paramyxovirus that causes severe encephalitis and respiratory diseases in humans. Despite the severe pathogenicity of this virus and its pandemic potential, not even a single type of molecular therapeutics has been approved for human use. Considering the role...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2076-2607/10/6/1181 |
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| author | Vinay Randhawa Shivalika Pathania Manoj Kumar |
| author_facet | Vinay Randhawa Shivalika Pathania Manoj Kumar |
| author_sort | Vinay Randhawa |
| collection | DOAJ |
| description | Nipah virus (NiV) is a recently emerged paramyxovirus that causes severe encephalitis and respiratory diseases in humans. Despite the severe pathogenicity of this virus and its pandemic potential, not even a single type of molecular therapeutics has been approved for human use. Considering the role of NiV attachment glycoprotein G (NiV-G), fusion glycoprotein (NiV-F), and nucleoprotein (NiV-N) in virus replication and spread, these are the most attractive targets for anti-NiV drug discovery. Therefore, to prospect for potential multitarget chemical/phytochemical inhibitor(s) against NiV, a sequential molecular docking and molecular-dynamics-based approach was implemented by simultaneously targeting NiV-G, NiV-F, and NiV-N. Information on potential NiV inhibitors was compiled from the literature, and their 3D structures were drawn manually, while the information and 3D structures of phytochemicals were retrieved from the established structural databases. Molecules were docked against NiV-G (PDB ID:2VSM), NiV-F (PDB ID:5EVM), and NiV-N (PDB ID:4CO6) and then prioritized based on (1) strong protein-binding affinity, (2) interactions with critically important binding-site residues, (3) ADME and pharmacokinetic properties, and (4) structural stability within the binding site. The molecules that bind to all the three viral proteins (NiV-G ∩ NiV-F ∩ NiV-N) were considered multitarget inhibitors. This study identified phytochemical molecules RASE0125 (17-O-Acetyl-nortetraphyllicine) and CARS0358 (NA) as distinct multitarget inhibitors of all three viral proteins, and chemical molecule ND_nw_193 (RSV604) as an inhibitor of NiV-G and NiV-N. We expect the identified compounds to be potential candidates for in vitro and in vivo antiviral studies, followed by clinical treatment of NiV. |
| first_indexed | 2024-03-09T22:59:53Z |
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| last_indexed | 2024-03-09T22:59:53Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-3f735b2caed74af1a4cce3d8404b024f2023-11-23T18:04:20ZengMDPI AGMicroorganisms2076-26072022-06-01106118110.3390/microorganisms10061181Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular DynamicsVinay Randhawa0Shivalika Pathania1Manoj Kumar2Virology Discovery Unit and Bioinformatics Centre, CSIR-Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, IndiaVirology Discovery Unit and Bioinformatics Centre, CSIR-Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, IndiaVirology Discovery Unit and Bioinformatics Centre, CSIR-Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, IndiaNipah virus (NiV) is a recently emerged paramyxovirus that causes severe encephalitis and respiratory diseases in humans. Despite the severe pathogenicity of this virus and its pandemic potential, not even a single type of molecular therapeutics has been approved for human use. Considering the role of NiV attachment glycoprotein G (NiV-G), fusion glycoprotein (NiV-F), and nucleoprotein (NiV-N) in virus replication and spread, these are the most attractive targets for anti-NiV drug discovery. Therefore, to prospect for potential multitarget chemical/phytochemical inhibitor(s) against NiV, a sequential molecular docking and molecular-dynamics-based approach was implemented by simultaneously targeting NiV-G, NiV-F, and NiV-N. Information on potential NiV inhibitors was compiled from the literature, and their 3D structures were drawn manually, while the information and 3D structures of phytochemicals were retrieved from the established structural databases. Molecules were docked against NiV-G (PDB ID:2VSM), NiV-F (PDB ID:5EVM), and NiV-N (PDB ID:4CO6) and then prioritized based on (1) strong protein-binding affinity, (2) interactions with critically important binding-site residues, (3) ADME and pharmacokinetic properties, and (4) structural stability within the binding site. The molecules that bind to all the three viral proteins (NiV-G ∩ NiV-F ∩ NiV-N) were considered multitarget inhibitors. This study identified phytochemical molecules RASE0125 (17-O-Acetyl-nortetraphyllicine) and CARS0358 (NA) as distinct multitarget inhibitors of all three viral proteins, and chemical molecule ND_nw_193 (RSV604) as an inhibitor of NiV-G and NiV-N. We expect the identified compounds to be potential candidates for in vitro and in vivo antiviral studies, followed by clinical treatment of NiV.https://www.mdpi.com/2076-2607/10/6/1181Nipah virusmolecular dockingsmall-molecule inhibitorsmolecular dynamicsdrug repurposingmultitarget inhibitor |
| spellingShingle | Vinay Randhawa Shivalika Pathania Manoj Kumar Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics Microorganisms Nipah virus molecular docking small-molecule inhibitors molecular dynamics drug repurposing multitarget inhibitor |
| title | Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics |
| title_full | Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics |
| title_fullStr | Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics |
| title_full_unstemmed | Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics |
| title_short | Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics |
| title_sort | computational identification of potential multitarget inhibitors of nipah virus by molecular docking and molecular dynamics |
| topic | Nipah virus molecular docking small-molecule inhibitors molecular dynamics drug repurposing multitarget inhibitor |
| url | https://www.mdpi.com/2076-2607/10/6/1181 |
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