Lead Identification for Severe Acute Respiratory Syndrome Coronavirus-2 Spike D614G Variant Of COVID-19: A Virtual Screening Process

Malathi Kullappan¹, Jenifer M Ambrose¹ and Surapaneni Krishna Mohan^2*

¹Department of Research, Panimalar Medical College Hospital and Research Institute, Varadharajapuram, Poonamallee, Chennai - 600 123, India.

²Departments of Biochemistry, Clinical Skills and Simulation, Research, Panimalar Medical College Hospital and Research Institute, Varadharajapuram, Poonamallee, Chennai - 600 123, India.

Corresponding Author E-mail: krishnamohan.surapaneni@gmail.com

Abstract: COVID-19, a pandemic disease caused by single-stranded RNA virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The structural spike (S) protein of SARS-CoV-2 plays a vital role in host cell entry, where the Angiotensin-Converting Enzyme-2 (ACE2) receptor of the human cell binds to the Receptor Binding Domain (RBD) region of the S1 domain and makes cell entry. The binding affinity of SARS-CoV-2-ACE2 is tenfold higher than the SARS-CoV-1-ACE2. Recent studies expose that the SARS-CoV-2 S D614G variant is highly infectious than D614 protein, also the D614G variant is highly stable than D614. So far, there is no effective viral-specific regimen for COVID-19. To overcome such problems, in our study, we have utilized the ZINC database to screen potent leads against the highly transmitting SARS-CoV-2 spike D614G protein, through a virtual screening procedure. We have applied three computational tools iGEMDOCK server, AutoDock version 4.2.6 and admetSAR to get active leads. The ZINC000150588351 (Elbasvir), ZINC000064540179 (Sofosbuvir analogue) and ZINC000137700912 (Sofosbuvir analogue) molecules have a greater binding affinity with the high binding energies of -8.22 kcal/mol, -8.13 kcal/mol and -7.64 kcal/mol respectively. The molecules ZINC000064540179 and ZINC000137700912 have high binding energy than their core molecule Sofosbuvir (ZINC100074252) of -4.06 kcal/mol. The ADMET prediction of these molecules reveals satisfactory human intestinal absorption and non-mutagenic property. Our results deliver valuable contributions to the design of inhibitors against COVID-19.

Keywords: Active lead; Binding Energy; COVID-19; Molecular docking; SARS-CoV-2; Virtual Screening

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