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. Graphical abstract Image 1 Highlights • Main protease (M pro ) 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 M pro of SARS-CoV-2. • Molecular dynamics stability analysis revealed that 2019-nCoV M pro – Akuammicine N-Oxide is stable. • Akuammicine N-Oxide may represent potential treatment options against M pro of 2019-nCoV.
【저자키워드】 COVID-19, SARS-CoV-2, main protease, molecular docking, Dynamics simulations, AYUSH-64, 【초록키워드】 Vaccine, pandemic, Anti-inflammatory, India, 2019-nCoV, drug, molecular dynamics, protease, in silico, binding energy, Molecular dynamics simulation, Epidemic, stability, Corona, management, Clinical studies, drug target, ingredient, molecular, respiratory, disease, anti-viral drug, AutoDock, Ligand, Interaction, Analysis, Image, health emergency, Clinical use, Abstract, enzyme, potential treatment option, complex, 6LU7, Compound, M pro, residues, material, Cys145, positive, Council, Public, PDB, objective, HIS164, Result, selected, highest, identify, performed, evaluate, the disease, approved, conducted, screened, were used, exhibit, docked, 【제목키워드】 protease, Compound, the SARS-CoV-2,