In late 2019, an outbreak of COVID-19 caused by SARS-COV-2 was declared a pandemic. The outbreak killed millions of people and caused economic instability in different countries due to movement restrictions. The pandemic may have ended, but there is a need to understand how to handle such cases better using already-approved molecules in the event of future occurrences. In this study, we utilized computational approaches to gain insight into the infestation mechanism of SARS-COV-2 and possible blockade with approved drugs. We obtained 2015 approved drugs from drugbank and representatives of the spike glycoprotein interaction with angiotensin-converting enzyme 2 (ACE2). We carried out sequence alignment of the spike glycoprotein of different SARS-COV-2 variants using clustal omega. We evaluated the amino acids involved in the viral attachment. We carried out molecular docking simulations in the selected interaction regions. Nine (9) interaction regions were found in the SARS-COV-2 spike bridge formation with ACE2. We undertook post docking and analysis and 2D visualization of selected docked complexes. The SARS-COV-2 spike glycoprotein variants were similar in the region of the spike protein interaction with the ACE2, except for the omicron variant. The top 20 frontrunner drugs on different interaction points were selected based on the mean values of the binding affinities obtained from molecular docking simulations. The visualization of top multitargeting drugs Dutasteride, Ergotamine, Folic acid, Piroxicam, Ketoconazole, Ceftriaxone, Amodiaquine and Methotrexate, revealed interactions that could possibly block SARS-COV-2 spike glycoprotein interaction with ACE2 receptor. Further studies will be carried out to observe the stability of the frontrunner complexes.