Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics
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Creator |
Randhawa, Vinay
Pathania, Shivalika Kumar, Manoj |
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Subject |
QR Microbiology
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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.
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Publisher |
MDPI
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Date |
2022-06-09
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Type |
Article
PeerReviewed |
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Relation |
https://www.mdpi.com/2076-2607/10/6/1181
http://crdd.osdd.net/open/2991/ |
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Identifier |
Randhawa, Vinay and Pathania, Shivalika and Kumar, Manoj (2022) Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics. Microorganisms, 10 (6).
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