Understandingthe binding interface between the virus and human receptors is pivotalto these efforts and paramount to curbing infection and transmission.Here we employ atomic force microscopy and steered molecular dynamicssimulation to explore SARS-CoV-2 receptor binding domain (RBD) variantsand angiotensin-converting enzyme 2 (ACE2), examining the impact ofmutations at key residues upon binding affinity. Here, ACE2 is linked to infection.