期刊
JOURNAL OF MOLECULAR STRUCTURE
卷 1229, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.molstruc.2020.129489
关键词
COVID-19; SARS CoV-2 main protease; Docking and molecular dynamics simulation; Vasaka Alkaloids
资金
- IIT Bhubaneswar
Using computational methods, this study found that an alkaloid (anisotine) from Justicia adhatoda leaf extracts exhibited good binding affinity to SARS CoV-2 Mpro, potentially making it a more potent inhibitor compared to the recommended antiviral drugs (lopinavir and darunavir). Further animal and patient experiments may validate anisotine as a promising anti-COVID-19 drug.
The COVID-19 pandemic, caused by SARS CoV-2, is responsible for millions of death worldwide. No approved/proper therapeutics is currently available which can effectively combat this outbreak. Several attempts have been undertaken in the search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro), key component for the cleavage of the viral polyprotein, is considered to be one of the important drug targets for treating COVID-19. Various phytochemicals, including polyphenols and alkaloids, have been proposed as potent inhibitors of Mpro. The alkaloids from leaf extracts of Justicia adhatoda have also been reported to possess anti-viral activity. But whether these alkaloids exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To explore this in detail, we have adopted computational approaches. Justicia adhatoda alkaloids possessing proper drug-likeness properties and two anti-HIV drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only one alkaloid (anisotine) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.9 kcal/mol). Molecular dynamic simulations (100 ns) revealed that Mpro-anisotine complex is more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bonds and MM-GBSA analysis suggested that anisotine is a more potent Mpro inhibitor than the two previously recommended antiviral drugs (lopinavir and darunavir) and may evolve as a promising anti-COVID-19 drug if proven in animal experiments and on patients. (C) 2020 Elsevier B.V. All rights reserved.
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