Computational identification of natural product leads that inhibit mast cell chymase: an exclusive plausible treatment for Japanese encephalitis

Kant, Kamal; Rawat, Ravi; Bhati, Vipin; Bhosale, Shailesh; Sharma, Dalchand; Banerjee, Subham; Kumar, Anoop

doi:10.1080/07391102.2020.1726820

Cited by 17 publications

(2 citation statements)

References 28 publications

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“…The molecular docking investigation was conducted using the PyRx-v0.8 virtual screening software, which featured AutoDock Vina with the Lamarckian genetic algorithm [ 86 , 87 , 88 , 89 ]. The active sites for the target proteins, 4CGS (Tyr102, Gly15, Arg140, Lys46, Lys16, Tyr14, Tyr58, Lys89, Asn101, Gly110, Gln60, Ser95, Phe85, Asp97, Asp107, Phe340, Tyr106, Gln339), 4CGP (Tyr294, Arg42, Leu291, Asn316, Tyr32, Arg82, Glu117, Val326, Gly119, Ala123, Arg132, Tyr124, Pro239, Arg167, Ile240, Asp121, Asp113, Val292, Phe118, Gly120, Asn293, Thr241, Ile318, Gly327), and 4CGQ (Leu115, Leu83, Tyr106, Asp107, Gly110, Tyr111, Met114, Arg140, Asn152, Ser177, Ser179, Glu181, Lys16, Val188, Lys219, Gln262, Asp113, Tyr102, Pro116, Arg270, Arg82, Thr300, Glu62, Tyr302) were identified through an extensive literature review [ 84 , 90 ] and were used in the docking approach.…”

Section: Methodsmentioning

confidence: 99%

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications

Arivuselvam,

Dera,

Parween Ali

et al. 2023

Antibiotics

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Prodigiosin pigment has high medicinal value, so exploring this compound is a top priority. This report presents a prodigiosin bioactive compound isolated from Serratia marcescens JSSCPM1, a new strain. The purification process of this compound involves the application of different chromatographic methods, including UV-visible spectroscopy, high-performance liquid chromatography (HPLC), and liquid chromatography–mass spectrometry (LC/MS). Subsequent analysis was performed using nuclear magnetic resonance (NMR) to achieve a deeper understanding of the compound’s structure. Finally, through a comprehensive review of the existing literature, the structural composition of the isolated bioactive compound was found to correspond to that of the well-known compound prodigiosin. The isolated prodigiosin compound was screened for antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound inhibited the growth of Gram-negative bacterial strains compared with Gram-positive bacterial strains. It showed a maximum minimum inhibitory concentration against Escherichia coli NCIM 2065 at a 15.9 ± 0.31 μg/mL concentration. The potential binding capabilities between prodigiosin and the OmpF porin proteins (4GCS, 4GCP, and 4GCQ) were determined using in silico studies, which are generally the primary targets of different antibiotics. Comparative molecular docking analysis indicated that prodigiosin exhibits a good binding affinity toward these selected drug targets.

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Section: Methodsmentioning

confidence: 99%

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications

Arivuselvam,

Dera,

Parween Ali

et al. 2023

Antibiotics

View full text Add to dashboard Cite

show abstract

“…MD simulation is crucial in drug design; it facilitates binding and catalytic mechanism prediction after identifying a molecule with a plausible propensity for a target [ 62 , 63 ]. Many researchers have indicated MD as crucial to refine, validate, and improve docking evaluation [ 61 , 64 ]. There are several commercial, non-commercial, and web-based MD simulation programs for molecular modeling studies [ 63 ] in which the AMBER suite [ 65 ] is a prominent one.…”

Section: Methodsmentioning

confidence: 99%

Allostery Inhibition of BACE1 by Psychotic and Meroterpenoid Drugs in Alzheimer’s Disease Therapy

et al. 2022

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In over a century since its discovery, Alzheimer’s disease (AD) has continued to be a global health concern due to its incurable nature and overwhelming increase among older people. In this paper, we give an overview of the efforts of researchers towards identifying potent BACE1 exosite-binding antibodies and allosteric inhibitors. Herein, we apply computer-aided drug design (CADD) methods to unravel the interactions of some proposed psychotic and meroterpenoid BACE1 allosteric site inhibitors. This study is aimed at validating the allosteric potentials of these selected compounds targeted at BACE1 inhibition. Molecular docking, molecular dynamic (MD) simulations, and post-MD analyses are carried out on these selected compounds, which have been experimentally proven to exhibit allosteric inhibition on BACE1. The SwissDock software enabled us to identify more than five druggable pockets on the BACE1 structural surface using docking. Besides the active site region, a melatonin derivative (compound 1) previously proposed as a BACE1 allostery inhibitor showed appreciable stability at eight different subsites on BACE1. Refinement with molecular dynamic (MD) simulations shows that the identified non-catalytic sites are potential allostery sites for compound 1. The allostery and binding mechanism of the selected potent inhibitors show that the smaller the molecule, the easier the attachment to several enzyme regions. This finding hereby establishes that most of these selected compounds failed to exhibit strong allosteric binding with BACE1 except for compound 1. We hereby suggest that further studies and additional identification/validation of other BACE1 allosteric compounds be done. Furthermore, this additional allosteric site investigation will help in reducing the associated challenges with designing BACE1 inhibitors while exploring the opportunities in the design of allosteric BACE1 inhibitors.

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Unravelling the natural dual-target inhibiting potential of cucurbit bioactive compounds for the management of cucumber mosaic virus (CMV) through computational approaches

2021

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Computational identification of natural product leads that inhibit mast cell chymase: an exclusive plausible treatment for Japanese encephalitis

Cited by 17 publications

References 28 publications

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications

Isolation, Identification, and Antibacterial Properties of Prodigiosin, a Bioactive Product Produced by a New Serratia marcescens JSSCPM1 Strain: Exploring the Biosynthetic Gene Clusters of Serratia Species for Biological Applications

Allostery Inhibition of BACE1 by Psychotic and Meroterpenoid Drugs in Alzheimer’s Disease Therapy

Unravelling the natural dual-target inhibiting potential of cucurbit bioactive compounds for the management of cucumber mosaic virus (CMV) through computational approaches

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