Molecular Docking Analysis of Chloroquine and Hydroxychloroquine and Design of Anti SARS-CoV2 Protease

Abstract

In this present investigation, a structure-based docking design technique was explored in designing a novel derivative of chloroquine for the treatment and management of new COVID 19 disease. To achieve this, the molecular docking simulation method was used to investigate the level of chloroquine and hydroxychloroquine (Drugs presently under clinical trial) interactions on SARSCoV2 enzyme (a causative agent of COVID 19 disease). Chloroquine and hydroxychloroquine which has been debated as drugs for the treatment of COVID 19 were subjected to molecular docking analysis, and the binding energies generated were found to be -6.1kcal/mol and -6.8 kcal/mol respectively. These two high binding energies revealed the binding strength of these two compounds against the SARS-CoV2 protease. Moreover, novel 2-((4-((7-chloroquinolin-4 yl) amino)pentyl)((methylamino)methyl)amino) ethan-1-ol as an anti-SARS-CoV2 protease was designed through the structural modification of hydroxychloroquine. The binding energy of this drug candidate was found to be -6.9 kcal/mol. This novel drug was found to bind and form hydrogen bonding with the binding site of SARS-CoV2 protease through GLU166, GLY143, PHE140, ASN142 and HIS163 amino acids. With this binding energy, this new drug candidate could bind better to the human SARS-CoV2 protease’ binding site. This research provides a clue for other scientists on various ways of designing and identify the types of amino acids that may be responsible for protein action on SARS-CoV2.

Funding: None to declare.

Declaration of Interest: None to declare.

Ethical: Not required.

Keywords: Molecular docking simulation, COVID 19, SARS-CoV2, CADD