Fragment Based Drug Design (FBDD) of an Exemplar Inhibitor Against Spike Glycoprotein of SARS-CoV-2

Abstract

COVID-19 outbreak has become an unprecedented healthcare crisis. To lessen the havoc of pandemic, several multidisciplinary efforts are continuously taken for treatment and precaution. The Fragment-Based Drug Design (FBDD) branch of Computational Aided Drug Discovery (CADD) was one of the methodologies used in current research, focused on the spike glycoprotein of the coronavirus. Fragments were dismembered from repurposed antivirals (FDA-approved) and the same was docked against PDB ID: 6VXX spike glycoprotein. The final inhibitor was docked against the spike glycoprotein and the dock score was recorded. Top scoring hits were identified and through a combinatorial library an exemplar inhibitor was designed. Affinity of an inhibitor towards protein was also observed, and docking score was recorded. Furthermore, the ADME properties were predicted for future development process. FBDD can be another approach to High Throughput Screening (HTS) for the generation of lead compounds for drug targets. This approach was applied to establish a new design computationally against SARS-CoV-2. Thus, additional research using fragments to create a different inhibitor could be done, saving time from working with, screening through, and filtering all sets of fragments, even in the antivirals section.