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Identification of alkaloids from Justicia adhatoda as potent SARS CoV-2 main protease inhibitors: An in silico perspective.
Ghosh, Rajesh; Chakraborty, Ayon; Biswas, Ashis; Chowdhuri, Snehasis.
  • Ghosh R; School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
  • Chakraborty A; School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
  • Biswas A; School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
  • Chowdhuri S; School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, India.
J Mol Struct ; 1229: 129489, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-2095816
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: J Mol Struct Year: 2021 Document Type: Article Affiliation country: J.molstruc.2020.129489

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: J Mol Struct Year: 2021 Document Type: Article Affiliation country: J.molstruc.2020.129489