Abul Bashar Ripon Khalipha1, 2*, Md. Shimul Bhuia1, Md. Milon Mundal1, Md. Solayman Hossain1, Musfiqur, Rahman Sakib1, Abdullah Al Shamsh Prottay1, Naimur Rahman1, Golam Rabbani1, Khadija Akter1.
1Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman
Science and Technology University, Gopalganj 8100, Bangladesh
2 Evergreen Scientific Research Centre, Gopalganj 8100, Bangladesh
Abstract
The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
originated in the Chinese city of Wuhan and has been spread worldwide. In a
life-threatening situation, where there is no specific and licensed anti-COVID
19 drug of choice available. Afzelin (AF) a natural compound from
Zanthoxylum bungeanum, having antiviral activity against SARS-CoV-2.
SARS-Cov-2 enters into the host cell through ACE2 and has a significant
binding affinity to ACE2. The higher binding affinity and adequate
pharmacokinetics of Afzelin have triggered us to design several new chemical
entities for the discovery and development of new compounds against SARS
CoV-2. In this study, we designed ligand-based drug strategies to select
potential target molecules to be an effective inhibitor of protein. AF and some
of its derivative
es (AF-Cl, AF-Br, AF-CF3, AF-OCH2CH3, AF-OCH2CF3) were screened
against ACE2 (PDB ID: 6M0J), RNA dependent RNA polymerase (PDB ID:
7BTF), the main protease (PDB ID: 6LU7), PLpro (PDB ID: 7KOL) crystal
structure of the protein. Molecular docking was performed under
AutoDockVina in PyRx platform to reveal noble scaffolds having the highest
binding affinity -9.2 for the modified drug AF-CF3 than the original drug AF
(-8.3) against 6M0J. Molecular orbital theory and discovery studio visualizer
v4.5.0.15071 were applied to get thermodynamically more stable and
chemically reactive compounds to find the nonbonding interactions and
binding sites of the proteins. The hydrogen bond, pi-alkyl bonds, preADMET
and admetSAR@LMMD online database have been utilized to predict the
pharmacokinetic properties and toxicity of Afzelin and its derivatives.
According to our findings, we proposed AF-CF3, will be a noble potential
inhibitor against ACE2 for the treatment of Covid-19.