Identifying Potential Inhibitors of SARS-CoV-2 from Three Medicinal Plants: An in silico Study

Abstract

Covid-19, caused by SARS-Cov-2, almost brought the world to a standstill due to its transmission from person to person, thereby leading to abrupt changes globally. The virus has utilized different mechanisms to get access into host tissues in order to enact its virulence. One of such is the ligation of its viral spike glycoproteins to the host’s angiotensin converting enzyme-2 (ACE-2) by transmembrane serine protease. Inhibitors of the ACE-2 have been reported to be useful in curtailing the spread of the virus. Medicinal plants have been reported to be used in different communities to fight the Covid disease. In this study, the inhibitory actions of 23 ligands selected from Stachytarpheta jamaicensis, Artemisia annua and Andrographis paniculata on ACE-2 were investigated using computer aided drug designing techniques. Grazoprevir was used as a reference ligand. The 3-D structures of the 24 ligands were retrieved from the PubChem database in their Structure Data Format (SDF). ACE-2 was retrieved in its Protein Data Bank (PDB) format. The protein and ligands were prepared and loaded for molecular docking algorithm. The reference drug and many ligands, especially from A. paniculata, exhibited good docking properties. 5-hydroxy-7, 2’, 6’trimethoxyflavone (CID 5318369) from A. paniculata, displayed binding energies of -7.4kcal/mol and 2 H bonds with Asn394 residue of the ACE-2 protein, and was thereafter subjected to molecular dynamics simulation at 70ns. After simulation, prominent H bonds were seen for Asn394, Gly395, Lys562 and Asn103. Phe40, Trp69, Leu120 and Phe390 showed hydrophobic interactions. The overall protein, ligand and complex dynamicity and conformational stability suggest that the interaction with the protein binding site region is highly preferable for the desired activity. In conclusion, this study demonstrated that the ligands from A. paniculata exhibited great docking properties against ACE-2. In particular, 5-Hydroxy-7, 2’, 6’trimethoxyflavone (CID 5318369) displayed good docking and molecular dynamics simulation results and is therefore recommended for clinical trials.