Dataset Information

Screening of phytoconstituents of Andrographis paniculata against various targets of Japanese encephalitis virus: An in-silico and in-vitro target-based approach.

ABSTRACT: Japanese encephalitis (JE) is one of the viral diseases affecting millions of peoples across the globe specifically developing countries. There is no specific treatment available, however, vaccines are available for its prevention. Unfortunately, available vaccines are not effective against all clinical isolates and are also associated with neurological complications in some individuals. We have screened the selected phytoconstituents of Andrographis paniculata against various targets of Japanese encephalitis virus (JEV) using Schrodinger suite 2019-3. Among all selected phytoconstituents, andrographolide has shown a good binding affinity towards NS3 protease as compared to NS3 helicase and NS5 Rdrp (RNA dependent RNA polymerase) of JEV. The molecular dynamics (MD) results have also shown good stability of andrographolide in the active site of NS3 protease. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis has also indicated a good pharmacokinetic and safety profile of andrographolide. Finally, the in-vitro target-based assay have confirmed the inhibitory potential of andrographolide against the NS3 protease of JEV. In conclusion, andrographolide could have the potential to develop as an antiviral agent against JEV through inhibition of protease, however, further investigations are required.

SUBMITTER: Bhosale S

PROVIDER: S-EPMC8663989 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Natural products derived from plants play a vital role in the discovery of new drug candidates, and these are used for novel therapeutic drug development. Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties. β-amyloid is a microscopic brain protein whose significant aggregation is detected in mild cognitive impairment and Alzheimer's disease (AD) brains. The accumulation of β-amyloid disrupts cell communication and triggers inflammation by activating immune cells, leading to neuronal cell death and cognitive disabilities. The proteases acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta secretase-1 (BACE-1) have been reported to be correlated with the synthesis and growth of β-amyloid plaques in the brains of AD patients. In the present study, the phenolic compounds from A. paniculata and S. paniculata that have been reported in the literature were selected for the current investigation. Furthermore, we employed molecular docking and molecular dynamics studies of the phenolic compounds with the proteins AChE, BChE, and BACE-1 in order to evaluate the binding characteristics and identify potent anti-amyloid agents against the neurodegenerative diseases such as AD. In this investigation, we predicted three compounds from A. paniculata with maximum binding affinities with cholinesterases and BACE-1. The computational investigations predicted that these compounds follow the rule of five. We further evaluated these molecules for in vitro inhibition activity against all the enzymes. In the in vitro investigations, 3,4-di-o-caffeoylquinic acid (5281780), apigenin (5280443), and 7-o-methylwogonin (188316) were found to be strong inhibitors of AChE, BChE, and BACE-1. These findings suggest that these compounds can be potent multi-target inhibitors of the proteases that might cumulatively work and inhibit the initiation and formation of β-amyloid plaques, which is a prime cause of neurotoxicity and dementia. According to our knowledge, these findings are the first report on natural compounds isolated from A. paniculata as multi-target potent inhibitors and anti-amyloid agents.

Dataset Information

Screening of phytoconstituents of Andrographis paniculata against various targets of Japanese encephalitis virus: An in-silico and in-vitro target-based approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets