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

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. 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. 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. 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. 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. [Display omitted] •Main protease (Mpro) is a molecular drug target for the 2019-nCoV of epidemic disease of COVID-19.•Docking strategies implemented to identify AUSH-64 having dual role as immunomodualtor and inhibition against Mpro of SARS-CoV-2.•Molecular dynamics stability analysis revealed that 2019-nCoV Mpro – Akuammicine N-Oxide is stable.•Akuammicine N-Oxide may represent potential treatment options against Mpro of 2019-nCoV.