Structure based Drug Designing Approaches in SARS-CoV-2 Spike Inhibitor Design

Abstract: The COVID-19 outbreak and the pandemic situation have hastened the research commu-nity to design a novel drug and vaccine against its causative organism, the SARS-CoV-2. The spike glycoprotein present on the surface of this pathogenic organism plays an immense role in viral entry and antigenicity. Hence, it is considered an important drug target in COVID-19 drug design. Several three-dimensional crystal structures of this SARS-CoV-2 spike protein have been identified and de-posited in the Protein DataBank during the pandemic period. This accelerated the research in com-puter-aided drug designing, especially in the field of structure-based drug designing. This review summarizes various structure-based drug design approaches applied to this SARS-CoV-2 spike pro-tein and its findings. Specifically, it is focused on different structure-based approaches such as mo-lecular docking, high-throughput virtual screening, molecular dynamics simulation, drug repurpos-ing, and target-based pharmacophore modelling and screening. These structural approaches have been applied to different ligands and datasets such as FDA-approved drugs, small molecular chemi-cal compounds, chemical libraries, chemical databases, structural analogs, and natural compounds, which resulted in the prediction of spike inhibitors, spike-ACE-2 interface inhibitors, and allosteric inhibitors.