Soubhagya K B

Molecular Docking Study of Potential Phytochemicals in Selected Pteridophytes and their Effects on the Complex of SARS-CoV2 Spike Protein with Human ACE2 1* Soubhagya K. B. & 2Dr. Benoj Mathew Research Scholar, PG & Research Department of Botany, St. Peter’s College, Kolenchery 2 Associate Professor, PG & Research Department of Botany, St. Peter’s College, Kolenchery 1 Abstract COVID-19 is a deadly infectious disease caused by the SARS-CoV-2 virus. In this alarming situation, being a rapid and cost effective method, in silco method of drug discovery plays a crucial role compared to the trial and error methods using experimental studies. Currently, Pharmaceutical research has effectively integrated molecular modeling methods to study complex biological and chemical systems in a variety of drug discovery programs. The incorporation of computational and experimental strategies has lead to the discovery of novel compounds. Molecular docking is a method that explores the ligand conformations adopted within the binding sites of macromolecular targets. The present study is aimed in a preliminary manner, to identify the potent phytochemicals that can inhibit the SARSCoV-2 spike protein through molecular docking studies, present in the three medicinally important pteridophytes that were selected randomly such as Adiantum capillus-veneris, Dicranopteris linearis and Psilotum nudum. Bioactive compounds present in them were screened based on previous literatures and were used as molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule using Mcule drug discovery platform. The study has identified the phytochemicals present in these pteridophytes which have significant docking scores and potential to inhibit SARS-CoV-2 infection. Among the 9 phytochemicals screened Astragalin, Amentoflavone and Hinokiflavone exhibited the highest negative docking score (-7.6, -7.9 and -7.4 respectively) which shows their higher affinity to the target, spike protein of SARS-CoV2. This depicts that these compounds can act as potential drug against the virus. Objectives    To study the phytochemicals present in different plants that has antiviral properties. To analyse the 3-D structure and binding sites of SARS-CoV-2 Spike protein. Application of Molecular Docking in virtual screening to predict binding affinity Methodology The SARS-CoV-2 S-proteincrystal structure of SARS-CoV-2 spike receptor-binding domain bound with ACE2(PDB ID:6M0J at 2.45Å) was downloaded from RCSB Protein Bank (PDB). Result Sl. No. Plant used Phytochemical studied Docking score 1 Adiantum capillusveneris Astragalin Caffeic acid -7.6 -4.6 2 Dicranopteris linearis Afzelin Isoquercitrin -6.0 -6.4 3 Psilotum nudum Quercitrin Amentoflavone Hinokiflavone -6.6 -7.9 -7.4 Kaemferol Quercetin -5.7 -6.2 Conclusion The main objective of ligand-receptor docking is to predict the predominant binding mode of a ligand with a receptor (protein) of a known 3-D structure. Binding Affinity is the capability of a specific ligand (small molecule) and the strength by which a compound interacts and binds to a target molecule's active sites. Lower the binding energy, greater the affinity of a ligand towards the receptor molecule. Thus, a compound with a higher negative value can be chosen as a viable drug candidate. This study provides insights into the mechanism of selective phytochemicals, when docked against one of the main target of SARS-CoV-2 ie., the spike protein. Among the total of 9 phytoconstituents screened virtually, 3 phytochemicals showed comparatively good inhibition on SARS-CoV-2 Spike protein 6M0J. These compounds displayed appreciable pharmacokinetic and physicochemical properties. Through analysis, it is concluded that phytochemicals Astragalin, Amentoflavone and Hinokiflavone exhibited the highest negative docking score from the plants Adiantum capillus-veneris and Psilotum nudum respectively. Thus, they can be considered as candidate inhibitors for targeted proteins and as drugs, after their in vitro and in vivo examinations. Overall, the computational predictions along with the reported pharmacological properties postulated that Astragalin, Amentoflavone and Hinokiflavone has potential against SARS-CoV-2 target proteins. The information generated may provide some insights into exploring for potential drugs against SARS-CoV-2 from plants, which can result in discovery of novel drugs. Reference The prediction of binding site was done with respect to the available literature and then verified using CAVER WEB (Jan stourac et al.,2019). The identified tunnels, their properties, energy profiles and trajectories for ligands’ passages were calculated and visualized. Phytochemicals with antiviral, antimicrobial, and antioxidant propertieswere screened based on the previous literature and were sorted, filtered. Drug-like compounds screened and was further fed into SWISS-ADME server for screening based on the pharmacokinetics, drug-likeliness, and medicinal chemistry friendliness of small molecules. For the purpose of study, mcule.com online platform was employed to carry out docking simulations. The MCULE purchasable (full) database was used.     Amaka Ubani, Francis Agwom, Nathan Yakubu Shehu, Pam Luka, Arinze Umera, Uzal Umar, Simeon Omale, Nnaemeka Emmanuel Nnadi, John Chinyere Aguiyi. 2020. Molecular Docking Analysis of Some Phytochemicals on Two SARS-CoV-2 Targets Potential Lead Compounds against Two Target Sites of SARS-CoV-2 Obtained from Plants. Pages 1,2. Basu A., Sarkar A. & Maulik U. 2020. Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2. Nature Publishing Group, UK. Pages 1-7. Kafila Kousar, Arshia Majeed, Farkhanda Yasmin, Waqar Hussain, Nouman Rasool. 2020. Phytochemicals from Selective Plants Have Promising Potential against SARSCoV-2: Investigation and Corroboration through Molecular Docking, MD Simulations,and Quantum Computations., Biomed Research International. vol. 2020. Pages 1-15. Khandelwal Alisha, Sharma Tripti. 2020. Computational Screening of Phytochemicals from Medicinal plants as COVID-19 Inhibitors. Pages 2-4