Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2

Selvaa Kumar C; Senthil Arun Kumar; Haiyan Wei

doi:10.1016/j.toxrep.2020.10.002

Comparative docking studies to understand the binding affinity of nicotine with soluble ACE2 (sACE2)-SARS-CoV-2 complex over sACE2

Toxicol Rep. 2020:7:1366-1372. doi: 10.1016/j.toxrep.2020.10.002. Epub 2020 Oct 8.

Authors

Selvaa Kumar C¹, Senthil Arun Kumar², Haiyan Wei²

Affiliations

¹ School of Biotechnology and Bioinformatics, D. Y. Patil Deemed to be University, Sector-15, CBD Belapur, Navi Mumbai, 400614, India.
² Department of Endocrinology and Metabolism, Genetics, Henan Children's Hospital (Children's Hospital Affiliated to Zhengzhou University), No-33, Longhu Waihuan East Road, Zhengzhou, 450018, China.

Abstract

The study aimed to validate the proficiency of nicotine binding with the soluble angiotensin-converting enzyme II receptor (sACE2) with or without SARS-CoV-2 in the context of its binding affinity. Modelled human sACE2 and the spike (S1) protein of Indian SARS-CoV-2 (INS1) docked with each other. On the other hand, nicotine docked with sACE2 in the presence or absence of SARS-CoV-2. Nicotine established a stable interaction with negatively charged Asp368 of sACE2, which in turn binds with amino acids like Thr362, Lys363, Thr365, Thr371, and Ala372. In the presence of nicotine, INS1 and sACE2 showed a reduced binding affinity score of -12.6 kcal/mol (Vs -15.7 kcal/mol without nicotine), and a lowered interface area of 1933.6 Å² (Vs 2057.3Å² without nicotine). The neuronal nicotinic acetylcholine receptor (nN-AChR) and angiotensin-converting enzyme 2 (ACE2) receptor showed 19.85% sequence identity among themselves. Following these receptors possessed conserved Trp302 and Cys344 amino acids between them for nicotine binding. However, nicotine showed a higher binding affinity score of -6.33 kcal/mol for the sACE2-INS1 complex than the sACE2 alone with -5.24 kcal/mol. A lowered inhibitory constant value of 22.95μM recorded while nicotine interacted with the sACE2-INS1 complex over the sACE2 alone with 151.69 μM. In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence.

Keywords: Neuronal nicotinic acetylcholine receptor; Nicotine; SARS-CoV-2; Smokers; Soluble ACE2; sACE2-INS1 complex.