IN- SILICO DISCOVERY OF NATURAL LEAD HITS FROM THE GENUS OF Arisaema AGAINST HUMAN RHINO VIRUS

Human rhino viruses (HRVs) serve as an imperative precursor for frequent cases of the common cold among children worldwide. An in-silico molecular docking attempt was made of some chief phytochemical entities (Arisaema plant species) as inhibitors of HRVs with selective therapeutic target action and minimal side effects. Around 60 phytoconstituents of different Arisaema species were docked against HRV receptor (PDB: 2XYA). Binding conformers of test ligands were compared with internal ligand. Finally, Syringaresinol 4'-O-β-D-glucopyranoside (glide score: 10.86), Rutin (glide score: -9.04) & Apigenin-6,8-di-C-β-D-glucopyranoside (glide score: -7.88) have resulted in most promising hits which can be further act as an effective template to experimentally validate or further designed their choosy and budding analogue agents against HRVSs.


INTRODUCTION
Presently, it is very imperative to mitigate the challenge of developing an antiviral drug for treatment of common cold.Common cold is a disease which is being caused by rhino viruses due to lack of specific treatment against this virus.Although, randomized therapy possess some better therapeutic effect but at the same time patients may also suffer from some adverse effects.
The symptom includes some cholinergic effect on the peripheral nervous system followed by nasal stuffiness, sneezing, cough & throat infections.If symptoms are not treated for longer time they may lead to some life threatening diseases such as chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis etc.On the light of literature findings, there is no specific antiviral drug which can cure the diseases which in turns extend the therapy as well as cost.School children's are generally more prone for this infection and repeatedly suffering with this disease.Nasal mucosa serves the main target for this virus.Mucous produced by the cilliary glands and goblet cells are generally contain metabolic cation and anion such as Cl -, Na, + ,K + , glycoprotein and immunoglobulin. 1These are responsible for resisting this infection & any kind of imbalance leads to infection in pulmonary cells.Currently, synthetic anti viral agents are still using in market but high cost & more adverse effects have twisted researchers focus on natural products.Globally, Herbal remedies have been researched under rigorous controls and have been approved by the Government of technologically advanced nations.There are different types of chemical entities in plants which are being accumulated as secondary metabolites during the course of biosynthesis. 2The nature of chemical entities varies due to dissimilar form of biosynthetic processes with particular time period of the plants.The literature findings have already reported excellent antiviral potential origin via natural products. 3isaema genus comprises of monocotyledon plant species belongs to family Araceae.Around 150 species are available throughout world, out of which 140 species are found in Asia, Africa, & Arab continents. 4 Previous studies have indicated that A. franchetianum showed promising bioactivity against porcine respiratory & reproductive syndrome virus (PRRSV). 5To date, very few species of Arisaema genus have been explored for their biological actions.Thus, present study was intended to computationally discover the in-silico lead hits from the genus of Arisaema against rhino virus.

Protein Preparation & Grid Configuration
The crystal structure of human rhino protein (PDB: 2XYA) was imported from RCSB protein bank in scrupulous PDB format. 6The protein was accounted in complex with 2-Phenylquinolin-4-ol as an internal standard.Protein preparation was initiated through protein pre-process pace which deals with the addition of polar hydrogen and removal of metal ions, cofactor and water molecule outside 5A 0 .Furthermore, ionization (pH: 6.7-7.3),optimization of hydrogen bond and restorative energy minimization steps were too applied to obtained the appropriate geometry of the receptor.The interactions potential of binding pocket were allotted through grid box formation near clicking around the active site of the internal ligand.

Ligand library
The reported chemical entities 3-D structures were sketched in Chem Draw Ultra 10.0 (Cambridge soft) in .molfile format and at last exported into Maestro software.Remarkably, ligands preparations were finished using least square OPLS_2005 force field followed by conformer generations & filtration to their energy minima with probable state creation (pH 7±2.0).

Docking computation
Extra precision (XP) glide docking was implemented on the generated receptor grid of human rhino virus protein.Finally, results outcome were analyzed via XP visualizer not only in the form of glide score but as well reviewing various probable interactions like H-bonding, π-π interactions & hydrophobic interactions, respectively. 25