title: In silico evaluation of inhibitory potential of triterpenoids from Azadirachta indica against therapeutic target of dengue virus, NS2B-NS3 protease.
abstract: OBJECTIVE
  NS2B-NS3 protease (NS2B-NS3 pro ) of dengue virus (DENV) is the prime therapeutic target for the development of anti-dengue drug to combat the DENV infection, which is currently an increasing health problem in many countries. In the area of antiviral drug discovery, numerous reports on the antiviral activity of various medicinal plants against dengue viruses have been published. Neem plant (Azadirachta indica) is one among those medicinal plants which is reported to show potential antiviral activity against DENV. But active principle of neem plant extract which has inhibitory potential against DENV NS2B-NS3 pro is not yet reported. The aim of the present study was to explore the inhibitory potential of five triterpenoids from neem plant, viz. nimbin, desacetylnimbin, desacetylsalannin, azadirachtin and salannin, against DENV NS2B-NS3 pro.
  
  
  METHODS
  The molecular 3D structural data of DENV NS2B-NS3 pro and selected triterpenoids of neem plant were collected from protein databank (PDB ID: 2VBC) and PubChem database respectively. The molecular docking approach was employed to find out the in silico inhibitory potential of the five triterpenoids against DENV NS2B- NS3 pro.
  
  
  RESULTS
  The molecular docking results showed that nimbin, desacetylnimbin and desacetylsalannin have good binding affinity with DENV NS2B-NS3 pro , while azadirachtin and salannin did not show any interaction with the target protein. It was observed that the DENV NS2B-NS3 pro binding energy for nimbin, desacetylnimbin and desacetylsalannin were -5.56, -5.24 and -3.43 kcal/mol, respectively.
  
  
  CONCLUSIONS
  The findings attained through this study on the molecular interaction mode of three neem triterpenoids and DENV NS2B-NS3 pro can be considered for further in vitro and in vivo validation for designing new potential drugs for DENV infection.
authors.affiliation: Faculty of Science and Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, Satna, Madhya Pradesh; Department of Biotechnology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, Uttar Pradesh, India.
authors.forename: Vivek Dhar
authors.initials: VD
authors.lastname: Dwivedi
authors.affiliation: Faculty of Science and Environment, Mahatma Gandhi Chitrakoot Gramodaya Vishwavidyalaya, Chitrakoot, Satna, Madhya Pradesh, India.
authors.forename: Indra Prasad
authors.initials: IP
authors.lastname: Tripathi
authors.affiliation: Department of Biotechnology, Deen Dayal Upadhyaya Gorakhpur University, Gorakhpur, Uttar Pradesh, India.
authors.forename: Sarad Kumar
authors.initials: SK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D031601:Azadirachta / Q000737:chemistry*; D003198:Computer Simulation; D003716:Dengue Virus / Q000201:enzymology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D064209:Phytochemicals; D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014315:Triterpenes; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases