In-silico molecular docking of Angiotensin-Converting Enzyme 2 receptor with selected inhibitors as potential anti SARS‐CoV 2 agent

Abstract

The functional receptor for SARS‐CoV 2, the newly discovered pathogen responsible for COVID-19, has been identified as angiotensin-converting enzyme 2 (ACE 2). This invariably suggests that blocking the ACE 2 active site could prevent the virus from gaining entrance into the cell to establish infection. The present study delineated the property of ACE 2 receptor and investigated the five (5) possible compounds that can inhibit its activity using molecular docking tools. The study revealed that the ACE 2 receptor has a molecular weight of 92491.05 Daltons, isoelectric pH 5.36, an aliphatic index of 80.55, instability index was predicted to be 40.10, and GRAVY value of −0.376. InterPro showed that ACE 2 has 19 amino acids used for substrate interaction. The motif and domain analysis done using different computational tools revealed that angiotensin-converting enzyme 2 is mainly found in the outer part of the cell membrane.  Multiple Em Motif Elicitation predicted that the sequences of ACE 2 have CQAAKHEGGHIKCDI in position 369–383, HDEDYCD at 195-201, MWGGFW at 270-275, VCNPDNW 132-138, KWRWMK 458-463, RSEVGKALR 169 -177,  VGAKNMNVRP, 244-253. The study revealed that trifluoperazine hydrochloride (TFH), a phenothiazine derivative compound, showed a minimum value of binding free energy as −7.90 kcal/mol while the inhibition constant was 1.62 µM. This suggests that this ligand (TFH) had the strongest interaction with ACE 2 when compared with other inhibitors screened. Quinine and thioridazine hydrochloride (TOH) another phenothiazine also exhibited a strong binding affinity for ACE 2, with the binding free energy of −6.54 kcal/mol and  −6.33 kcal/mol and inhibition constants (Ki) of 16.20 µM and 22.7 µM respectively. Pentamidine isethionate and allicin both interacted with the active site of ACE 2 receptors and inhibited with binding free energy and inhibition constants (Ki) of −3.94 kcal/mol and 1.29 mM; −3.65 kcal/mol and 2.12 mM respectively. Swiss Institute of Bioinformatics, Switzerland (ADME) analysis established that allicin satisfies the Lipinski’s rule with the Molecular Weight of 162.27(g/mol) (< 500), the lipophilicity of 1.18 (MLog P) ( < 5), hydrogen bond donors of 0 (< 5 ) and hydrogen bond acceptors of 1 (<10). This study suggests that trifluoperazine hydrochloride, thioridazine hydrochloride, quinine, and allicin could be possible ACE 2 receptor blockers that can be harnessed to prevent SARS-CoV 2 access into the cell of the host and allicin as a probable drug for COVID-19 patients.