The ability of coronaviruses infecting humans is invariably associated with their binding strengths to human receptor proteins. Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor of human cells. To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis, on the “hotspot” residues at protein-protein interfaces, by relative free energy calculations. Our results suggested that the binding strengths of SARS-CoV and SARS-CoV-2 to the host receptor are comparable. Free energy calculations showed a promise in assessing the infectious ability of viruses on a physical basis, and can also provide useful information for the design of antiviral drugs.