Taken together, our data demonstrate that the mechano-regulated dissociation kinetics (e.g., optimal lifetime at 10 pN) of SARS2-S with ACE2 best correlates with viral infection efficiency (Fig. 4n, o), in contrast to the in-situ or in-solution binding affinity (Fig. 4l, m), suggesting the essential role of force-strengthened spike/ACE2 binding in regulating SARS2 viral infection. Here, ACE2 is linked to viral infectious disease.