Further, we compared ACE2-RBD/Naltrexone binding affinity with some recently reported potential ACE2-RBD inhibitors. Both (SSAA09E2 and Bisoctrizole) displayed an affinity score of −6.7 kcal/mol and −8.5 kcal/mol respectively with the ACE2-RBD complex as compared to Naltrexone which shows an affinity score of −6.01 kcal mol−1 (Figure S3). Comparative analysis of docked conformation of two reported inhibitors as compared to Naltrexone revealed that the former two prefers to occupy the inner central cavity in ACE2-RBD complex (close to the N-terminus contact interface) and while Naltrexone occupied the core central surface with a greater number of contacts with the RBD of SARS Cov-2. As Naltrexone occupies the central interface of ACE2-RBD complex, thus, it can be expected to break a greater number of crucial contacts which in turn can inhibit the binding of RBD to host receptor ACE2. Further in-vitro and in-vivo studies are required to understand the efficacy of these compounds to understand the molecular basis of anti-coronavirus activity or inhibitory potential.