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The coronavirus disease 2019 main protease inhibitor from Andrographis paniculata (Burm. f) Ness

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has attracted worldwide attention. Andrographis paniculata (Burm. f) Ness (AP) is naturally used to treat various diseases, including infectious diseases. Its Andrographolide has been clinically observed for anti-HIV and has also in silico tested for COVID-19 main protease inhibitors. Meanwhile, the AP phytochemicals content also provides insight into the molecular structures diversity for the bioactive discovery. This study aims to find COVID-19 main protease inhibitor from AP by the molecular docking method and determine the toxicity profile of the compounds. The results obtained two compounds consisting of flavonoid glycosides 5,4'-dihydroxy-7-O-? -D-pyran-glycuronate butyl ester and andrographolide glycoside 3-O-?-D-glucopyranosyl-andrographolide have lower free binding energy and highest similarity in types of interaction with amino acid residues compared to its co-crystal ligands (6LU7) and Indinavir or Remdesivir. The toxicity prediction of the compounds also reveals their safety. These results confirm the probability of using AP phytochemical compounds as COVID-19 main protease inhibitors, although further research must be carried out.

SUBMITTER: Sukardiman

PROVIDER: S-EPMC7784943 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:Andrographis paniculata, commonly known as kalmegh is among the most popular medicinal herbs in Southeast Asia. It is widely cultivated for medicinal purposes. The bioactive molecule, Andrographolide accumulated in herb leaves has immense therapeutic and economic potential. However, comprehensive information regarding genetic diversity is very limited in this species. The present study assessed genetic diversity between and within the six populations (ecotypes) of twenty-four kalmegh accessions using multiple datasets (agro-morphological traits, phytochemical traits, and genic markers). This is the established report where EST-SSR (Expressed sequence tags-Simple Sequence Repeat) markers have been used to unlock genetic variation in kalmegh. Here, we identified and developed ninety-one metabolic pathway-specific EST-SSR markers. Finally, 32 random EST-SSR primer pairs were selected for genetic diversity assessment. Multivariate analysis to unveil the agro-morphological, phytochemical and genotypic variability was helpful in discriminating various germplasms studied in the present study. Among all the morphological discriptors used in present study, days to fifty percent flowering and dry herb yield were found as potential selection index for AP genetic improvement. Hierarchical cluster analysis built with agro-morphological data identified three major groups. However, corresponding analysis with phytochemical and molecular data generated two clear-cut groups among the studied individuals. Moreover, the grouping of individuals into different clusters using multiple datasets was geographically independent, and also showed inconsistency in grouping among agromorphological, phytochemical and molecular dataset based clusters. However, joint analysis using agro-morphological, phytochemical and genotypic information generated two genetic groups, which could be a valuable resource for identifying complementary crossing panels in the kalmegh breeding program. The accessions AP7, AP13, AP5, AP3 belong to cluster I and accessions AP17, AP18 belong to cluster II could be utilized as potential donors for high dry herb yield and andrographolide content, respectively in different selective breeding programs of AP. Thus, our results provided useful information about the overall genetic diversity and variation in economic traits useful for initiating selective breeding programs for contrasting traits of interest and maximizing genetic gain in kalmegh.

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.

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The coronavirus disease 2019 main protease inhibitor from Andrographis paniculata (Burm. f) Ness

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