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

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-6 4 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, antipyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-6 4 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (M-pro; 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 M-pro of SARS-CoV-2. Results: Among 36 compounds of four ingredients of AYUSH-6 4 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 M-pro 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 M-pro- 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 M-pro residues, Cys145, and His164. Conclusion: The results provide lead that, the presence of M-pro- Akuammicine N-Oxide with highest M-pro 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. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Institute of Transdisciplinary Health Sciences and Technology and World Ayurveda Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

The study evaluated the compounds in AYUSH-64 drug against SARS-CoV-2, with findings showing 35 compounds had good binding energies and Akuammicine N-Oxide was the most effective compound with strong affinity and interactions. These results suggest that AYUSH-64 could be a potential candidate for managing COVID-19.