In silico evaluation of the compounds of the ayurvedic drug, AYUSH-64, for the action against the SARS-CoV-2 main protease

Autor: Thrigulla Saketh Ram, Manne Munikumar, Vankudavath Naik Raju, Parasannanavar Devaraj, Naveen Kumar Boiroju, Rajkumar Hemalatha, P.V.V. Prasad, Manohar Gundeti, Brijesh S. Sisodia, Sharad Pawar, G.P. Prasad, Mukesh Chincholikar, Sumeet Goel, Anupam Mangal, Sudesh Gaidhani, N. Srikanth, K.S. Dhiman
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Ayurveda and Integrative Medicine, Vol 13, Iss 1, Pp 100413- (2022)
Druh dokumentu: article
ISSN: 0975-9476
DOI: 10.1016/j.jaim.2021.02.004
Popis: Background: Outbreak of Corona Virus Disease in late 2019 (COVID-19) has become a pandemic global Public health emergency. Since there is no approved anti-viral drug or vaccine declared for the disease and investigating existing drugs against the COVID-19. Objective: AYUSH-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences, India, has been in clinical use as anti-malarial, anti-inflammatory, anti-pyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-64 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (Mpro; PDB ID: 6LU7) via in silico techniques. Materials and methods: Different molecular docking software's of Discovery studio and Auto Dock Vina were used for drugs from selected AYUSH-64 compounds against SARS-CoV-2. We also conducted 100 ns period of molecular dynamics simulations with Desmond and further MM/GBSA for the best complex of AYUSH-64 with Mpro of SARS-CoV-2. Results: Among 36 compounds of four ingredients of AYUSH-64 screened, 35 observed to exhibits good binding energies than the published positive co–crystal compound of N3 pepetide. The best affinity and interactions of Akuammicine N-Oxide (from Alstonia scholaris) towards the Mpro with binding energy (AutoDock Vina) of −8.4 kcal/mol and Discovery studio of Libdock score of 147.92 kcal/mol. Further, molecular dynamics simulations with MM-GBSA were also performed for Mpro– Akuammicine N-Oxide docked complex to identify the stability, specific interaction between the enzyme and the ligand. Akuammicine N-Oxide is strongly formed h-bonds with crucial Mpro residues, Cys145, and His164. Conclusion: The results provide lead that, the presence of Mpro– Akuammicine N-Oxide with highest Mpro binding energy along with other 34 chemical compounds having similar activity as part of AYUSH-64 make it a suitable candidate for repurposing to management of COVID-19 by further validating through experimental, clinical studies.
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