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

JB Minari, KO Adekoya, CI Ayolabi, SA Adesida, VO Osunkalu, OO Adewumi, EE Agho, FD Adebiyi, BO Sholaja


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.

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