Introduction: SAR-CoV-2, the virus causing the novel coronavirus disease (Covid-19) and global pandemic, is associated with severe complications and mortality. The WHO has identified five variants of concern (VOCs), with the Alpha, Beta, Gamma, Delta, and Omicron being widespread across the world. SARS-CoV-2 is also capable of random mutations, with its genetic alterations affecting the viral phenotype and influencing transmissibility, virulence, and clinical severity. Exhibiting that the virus is prone to resisting antiviral therapies and vaccines. The uncertainties about the status of SARS-CoV-2 and the future of the pandemic, the inadequacy of the present vaccines and treatments, and the likelihood for further variants of concerns require further investigation on drug repurposing that can be used to treat Covid-19. Method:In this study, we investigate 30 potential Alzheimer Disease related molecules in targeting SARS-CoV-2 main protease (Mpro) (PDB ID: 6LU7) using molecular docking in Schrodinger Suites and Gromac’s molecular dynamic simulation and MMPBSA calculationswere simulated on the top 5 XP Glide compounds of interest to provide novel theoretical insights in possible promising targeting candidates. Results: The results revealed Pubchem CID: 71059746 (Glide Score: -7.256 kcal/mol and XP Gscore: -6.509 kcal/mol) has the best binding affinity and stable ligand-protein interaction in molecular dynamic simulation from the data set. Conclusion:While multiple molecules of interest were used to predict promising low binding energies one molecule, CID: 71059746 stood out. Furthermore, molecular dynamic and MMPBSA were carried out revealing favorable conditions. These compounds should be further studied in an effort to repurpose known molecules in counteracting COVID-19.

SARS-CoV-2; COVID-19; COVID; Drug Repurposing; Drug Discovery; Molecular Docking; Molecular Dynamic; Virtual Screening; Alzheimer’s Disease