An in silico Drug Repurposing Study to Inhibit the Spike Protein of SARS-CoV2

SARS-CoV2 has caused the recent mortal pandemic known as COVID-19. The drug repurposing approach can be employed to find the potential drugs capable of binding SARS-CoV2 structural and nonstructural proteins. The present study aimed to repurpose some common FAD-approved antiviral and non-antiviral drugs computationally for SARS-CoV2 treatment. In the in silico study, 89 FDA-approved drugs and Remdesivir, as the control, were analyzed by molecular docking to inhibit the SARS-CoV2 spike (S) protein as the key player in virus-cell binding. First, the Uniport website was used to find receptor and ganglioside binding domains (RBD and GBD, respectively) of the S protein as the target. The structure of the target was downloaded from RCSB, and 'the ligands' structures were downloaded from PubChem. All structures were refined using SPDV and PyRx software. AutoDock Vina was employed for the docking process. The result showed that 8 drugs, including Ledipasvir, Montelukast, Domperidone, Aprepitant, Folic acid, Losartan, Ticagrelor, and Rivaroxaban, can bind S protein and then inhibit the protein function. In addition, Ledipasvir, Montelukast, and Domperidone can bind GBD of the S protein with higher binding energy (-8.2, -8, -7.9 kcal/mol, respectively). On the other hand, higher RBD binding energy was calculated for Ticagrelor (-6.9 kcal/mol), Folic acid, Montelukast, and Domperidone (-6.5 kcal/mol). Generally, the ligands could inhibit GBD more than RBD. According to the binding energy to S protein and low side effects of the studied medications, Ledipasvir and Losartan can be introduced as the most effective candidates for repurposed drugs. Also, Gly496 and Asn137 are the most engaged amino acids in the ligand-receptor interaction from RBD and GBD, respectively.