International Journal of Evergreen Scientific Research Vol.04, Issue 02 (2021), pp.01-12 Research Paper ISSN:2664-2409(Print) 77 Copyright ESRC | All Rights Reserved © 2018-2022 Web link: https://ijesrc.com/ In-silico drug design of Zeylanone and its derivatives against 6M0J for treatment of COVID-19 using molecular docking tools Md. Shimul Bhuia 1 , Abul Bashar Ripon Khalipha 1,3* , Naimur Rahman 1 , Md. Golam Rabbani 1 , Md. Sajjad Hossain Siam 1 , Md. Solayman Hossain 1 , Milon Mondal 1 , Md. Hanif Munshi 2 , Md. Mozno Mia 2 , Shahadat Hossen 2 1 Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj-8100, Bangladesh 2 Department of Applied Chemistry and Chemical Engineering, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj-8100, Bangladesh 3 Evergreen Scientific Research Centre, Gopalganj-8100, Bangladesh Keyword: Zeylanone, Covid-19, Molecular modeling, SARS-CoV-2, Virtual screening, 6M0J, ACE2 Received: 02-08-2021 Accepted: 14-08-2021 Published: 30-10-2021 *Corresponding Author: Abul bashar Ripon Khalipha Email- khalipha1982@gmail.com Abstract: The pandemic COVID-19 resulted from the infection of the severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has become the most emergent global health issue. Particular and efficient antiviral therapy against SARS-Cov-2 is still lacking, so the refinement of effective antiviral drugs against the virus is urgently needed. The phytochemical Zeylanone (D) extracted from Plumbago zeylanica has strong antiviral activity with other pharmacological effects. SARS-Cov-2 affects the individual host cell because of its strong binding affinity with ACE2 of the lung’s epithelial cells by which the virus enters the host cell. Zeylanone contains a great inhibitory effects against the virus due to its attaching affinity with the same receptor (ACE2). The aim of this study is to design better conformer due to the adequate potency and suitable pharmacokinetics of Zeylanone. We have designed several derivatives and docked them against potential targets such as ACE2 (PDB ID: 6M0J), the main protease (PDB ID: 6LU7), RNA dependent RNA polymerase (PDB ID: 7BTF) and PLpro (PDB ID: 7KOL) crystal structures of proteins collected from the RCSB PDB protein data bank. AutoDockVina was used for docking, and drug-likeness, toxicity, carcinogenicity as well as pharmacokinetic properties were evaluated using PreADMET, SwissDrugDesign, and the admetSAR@LMMD online database. The interaction site between drugs and proteins, pocket size, type and distance of non-bond interaction were assessed by PyMOL and Discovery Studio visualizer v4.5.0.15071. Finally, all of the compounds were optimized, and their thermodynamic data were computed using Gauss View (v5.0). According to our findings, the derivative D3 has the highest binding value of -10.1 kcal/mol against 6M0J (ACE2), while the parent drug has a binding value of -8.9 kcal/mol against the same target. The derived drugs formed drug- protein complexes with various non-bond interactions for example conventional hydrogen bonds, alkyl bonds, pi-alkyl bonds, and pi-pi T-shaped bonds. All the derivatives ensured us of their non-toxicity and better pharmacokinetics than the parent drug. According to our investigation results, D3 (derived drug) can be referred to as a prospective novel inhibitor against ACE2 for the maintenance and treatment of viral affected patients.