BACKGROUND Different approaches have been proved effective for combating the COVID-19 pandemic. Accordingly, in silico drug repurposing strategy, has been highly regarded as an accurate computational tool to achieve fast and reliable results. Considering SARS-CoV-2's structural proteins and their interaction the host's cell-specific receptors, this study investigated a drug repurposing strategy aiming to screen compatible inhibitors of FDA-approved drugs against viral entry receptors (ACE2 and CD147) and integral enzyme of the viral polymerase (RdRp). METHODS The study screened the FDA-approved drugs against ACE2, CD147, and RDRP by virtual screening and molecular dynamics (MD) simulation. RESULTS The results of this study indicated that five drugs with ACE2, four drugs with RDRP, and seven drugs with CD147 achieved the most favorable free binding energy (ΔG < -10). This study selected these drugs for MD simulation investigation whose results demonstrated that ledipasvir with ACE2, estradiol benzoate with CD147, and vancomycin with RDRP represented the most favorable ΔG. Also, paritaprevir and vancomycin have good binding energy with both targets (ACE2 and RdRp). CONCLUSIONS Ledipasvir, estradiol benzoate, and vancomycin and paritaprevir are potentially suitable candidates for further investigation as possible treatments of COVID-19 and novel drug development.