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

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

doi:10.1016/j.jaim.2021.02.004

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

J Ayurveda Integr Med. 2022 Jan-Mar;13(1):100413. doi: 10.1016/j.jaim.2021.02.004. Epub 2021 Feb 25.

Authors

Thrigulla Saketh Ram¹, Manne Munikumar², Vankudavath Naik Raju³, Parasannanavar Devaraj⁴, Naveen Kumar Boiroju⁴, Rajkumar Hemalatha⁴, P V V Prasad¹, Manohar Gundeti⁵, Brijesh S Sisodia⁶, Sharad Pawar⁷, G P Prasad⁷, Mukesh Chincholikar⁸, Sumeet Goel⁸, Anupam Mangal⁸, Sudesh Gaidhani⁸, N Srikanth⁸, K S Dhiman⁸

Affiliations

¹ CCRAS-National Institute of Indian Medical Heritage, Revenue Board Colony, Gaddiannaram, Hyderabad, 500036, Telangana State, India.
² NIN-TATA Centre for Excellence in Public Health Nutrition, ICMR-National Institute of Nutrition, Hyderabad, 500007, Telangana State, India. Electronic address: mannemunikumar.bioinfo@gmail.com.
³ Nutrition Information, Communication & Health Education (NICHE), ICMR-National Institute of Nutrition, Hyderabad, 500007, Telangana State, India.
⁴ ICMR-National Institute of Nutrition, Hyderabad, 500007, Telangana State, India.
⁵ CCRAS-Raja Ramdeo Anandilal Podar (RRAP) Central Ayurveda Research Institute for Cancer, Mumbai, India.
⁶ CCRAS-Regional Ayurveda Research Institute for Drug Development, Gwalior, India.
⁷ CCRAS-Regional Ayurveda Institute for Fundamental Research, Pune, India.
⁸ Central Council for Research in Ayurvedic Sciences, New Delhi, India.

Abstract

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 (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-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 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.

Keywords: AYUSH-64; COVID-19; Dynamics simulations; Main protease; Molecular docking; SARS-CoV-2.