Multi-step molecular docking and dynamics simulation-based screening of large antiviral specific chemical libraries for identification of Nipah virus glycoprotein inhibitors

Kalbhor, Malti Sanjay; Bhowmick, Shovonlal; Alanazi, Amer M.; Patil, Pritee Chunarkar; Islam, Ataul

doi:10.1016/j.bpc.2020.106537

Cited by 21 publications

(18 citation statements)

References 40 publications

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“…The data on ligand-binding sites in all three viral proteins were obtained from the published literature. The binding-site residues of protein NiV-G (Gln559, Glu579, Tyr581, Ile588) were obtained from Kalbhor et al (2021) [46], while binding-site residues of NiV-F (His29, Tyr30, Val39, Lys40, Asn380, Tyr432, Leu433) and NiV-N (Lys34, Arg36, Phe38, Val58, Ala65, Ser67, Glu124, Leu128, Ile131) were obtained from Sen et al (2019) [47]. To assess the conformational/structural differences among the ligand-binding pockets in the viral protein structures, their respective pocket volume sizes were assessed using Pocket Volume Measurer (POVME) [48] and Pymol software.…”

Section: Assessment Of Ligand-binding Pocketsmentioning

confidence: 99%

“…The data on ligand-binding sites in all three viral proteins were obtained from the published literature. The binding-site residues of protein NiV-G (Gln559, Glu579, Tyr581, Ile588) were obtained from Kalbhor et al (2021) [46]. The residues Ile588 and Tyr581 participate in hydrophobic interactions and contribute to the binding pocket that accommodates Phe120 of human EFNB2; hence, they are considered critical for inhibiting interactions by which NiV attach to EFN receptors [62].…”

Section: Volumetric Analyses Of Ligand-binding Protein Pocketsmentioning

confidence: 99%

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Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics

2022

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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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Section: Assessment Of Ligand-binding Pocketsmentioning

confidence: 99%

“…The data on ligand-binding sites in all three viral proteins were obtained from the published literature. The binding-site residues of protein NiV-G (Gln559, Glu579, Tyr581, Ile588) were obtained from Kalbhor et al (2021) [46]. The residues Ile588 and Tyr581 participate in hydrophobic interactions and contribute to the binding pocket that accommodates Phe120 of human EFNB2; hence, they are considered critical for inhibiting interactions by which NiV attach to EFN receptors [62].…”

Section: Volumetric Analyses Of Ligand-binding Protein Pocketsmentioning

confidence: 99%

Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics

2022

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“…The energy minimized full system was set for the production run at a temperature of 300K and pressure of 1 bar. The isotherm-isobar (NPT) ensemble was selected and simulation was carried out for 100 ns [29,34,43,67].…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Phytochemicals as Potential Drug Candidates for SARS Cov-2: An RDRp Based In-Silico Drug Designing

Joy¹,

Cyriac²

2022

Proceedings of the Conference BioSangam 2022: Emerging Trends in Biotechnology (BIOSANGAM 2022)

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The global pandemic that the world is currently witnessing, COVID-19, even with vaccines available, the test positivity rate (TPR) tends to remain highly threatening. This research focuses on identifying phytochemicals, previously known for their broad-spectrum antiviral properties which can be potential drug candidates for theSARS-CoV-2. A total of 225 phytocompounds (downloaded from PubChem database) are docked against targetprotein (downloaded from PDB database) of SARS-CoV-2using the POAP pipeline. The target protein is the RDRp complex. They are screened according to their binding affinity values and the filtered phytochemicals are then subjected to various analyses including ADME properties (preADMET, swissADME), bioactivity score, and molecular properties (molinspiration), drug-likeness (preADMET), lipophilicity, water solubility, and pharmacokinetics (swissADME). The receptor-ligand interactions and the amino acid positions are obtained using Discovery Studio Visualiser. Molecular dynamic simulation studies are performed to reveal key receptor-drug interactions that must be formed to achieve tight drug binding and also to predict stability. Out of the 225, 10 phytochemicals showed the best scores and more probability of drug action. Compounds that showed promising drug action potential include oriciacridone, corilagin, cinchophyllamine, sophaline D, amentoflavone, cryptomisrine, ginkgetin, hypericin, pseudojervine, dieckol, hinokiflavone, robustaflavone, solamargine. The research herein provides new possibilities for in vitro and in vivo analyses of the proposed ligands to develop new drugs againstSARS-CoV-2.

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“…Researchers discovered that the G protein is more important to Nipah infection than its fusion protein, whereas the fusion protein in Hendra is the main component of membrane attachment [ 100 ]. Molecular docking studies have been used to find common peptides that may inhibit the binding of glycoproteins on the surface of the Nipah virus [ 101 ]. Naturally occurring human antibodies have also been found to inhibit Hendra when given to infected animals [ 102 ]; interestingly, some of these monoclonal antibodies that neutralize Hendra also inhibit Nipah infection, with less reliability [ 102 ].…”

Section: Potential Prophylactic and Therapeutic Applications Of Gags In The Treatments Of Viral Zoonotic Diseasesmentioning

confidence: 99%

Implications of Glycosaminoglycans on Viral Zoonotic Diseases

2021

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Zoonotic diseases are infectious diseases that pass from animals to humans. These include diseases caused by viruses, bacteria, fungi, and parasites and can be transmitted through close contact or through an intermediate insect vector. Many of the world’s most problematic zoonotic diseases are viral diseases originating from animal spillovers. The Spanish influenza pandemic, Ebola outbreaks in Africa, and the current SARS-CoV-2 pandemic are thought to have started with humans interacting closely with infected animals. As the human population grows and encroaches on more and more natural habitats, these incidents will only increase in frequency. Because of this trend, new treatments and prevention strategies are being explored. Glycosaminoglycans (GAGs) are complex linear polysaccharides that are ubiquitously present on the surfaces of most human and animal cells. In many infectious diseases, the interactions between GAGs and zoonotic pathogens correspond to the first contact that results in the infection of host cells. In recent years, researchers have made progress in understanding the extraordinary roles of GAGs in the pathogenesis of zoonotic diseases, suggesting potential therapeutic avenues for using GAGs in the treatment of these diseases. This review examines the role of GAGs in the progression, prevention, and treatment of different zoonotic diseases caused by viruses.

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Multi-step molecular docking and dynamics simulation-based screening of large antiviral specific chemical libraries for identification of Nipah virus glycoprotein inhibitors

Cited by 21 publications

References 40 publications

Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics

Computational Identification of Potential Multitarget Inhibitors of Nipah Virus by Molecular Docking and Molecular Dynamics

Phytochemicals as Potential Drug Candidates for SARS Cov-2: An RDRp Based In-Silico Drug Designing

Implications of Glycosaminoglycans on Viral Zoonotic Diseases

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