The interaction of ACE2 with the RBD of Sars-Cov-2 spikes of Wuhan-Hu-1, B.1.1.7 and B.1.351 variants were examined in silico. In order to prevent complex formation between spike RBD and ACE2, the interactions of some candidate molecules and a standard drug with RBD were investigated. When the interactions of RBDs and ligands were analyzed in terms of hydrogen bonds and Gibbs free energies, Glucosamine and N-Acetyl-D-Galactasomine for Wuhan-Hu-1, Glucosamine for B.1.1.7 and Paxlovid for B.1.351 variants were found to be adventageous inhibitors.,Angiotension-converting enzyme 2 (ACE2) is the host receptor of the serious-acute respiratory syndrome coronavirus 2 (Sars-CoV-2) spike protein. In this article, the interaction of ACE2 with the receptor binding domains (RBD) of Wuhan-Hu-1 and United Kingdom (UK) and South African (SA) variants is examined in silico. Their Gibbs free energies were computed using a protein binding energies prediction model. The interaction characteristics of RBDs with possible inhibitory compounds as well as a standard drug, Paxlovid, were also investigated, and Gibbs free energies were computed. Molecular modeling, molecular dynamics and molecular docking methods were employed and the results are compared and discussed.