Quantifying the adhesive strength between the SARS-CoV-2 S-proteins and human receptor and its effect in therapeutics

The binding affinity and adhesive strength between the spike (S) glycoproteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the human angiotensin-converting enzyme 2 (ACE2) receptor is computed using molecular dynamics (MD) simulations. The calculations indicate that the binding affinity is [Formula: see text] [Formula: see text] with a maximum adhesive force of [Formula: see text] pN. Our analysis suggests that only 27 (13 in S-protein, 14 in ACE2) residues are active during the initial fusion process between the S-protein and ACE2 receptor. With these insights, we investigated the effect of possible therapeutics in the size and wrapping time of virus particles by reducing the binding energy. Our analysis indicates that this energy has to be reduced significantly, around 50% or more, to block SARS-CoV-2 particles with radius in the order of [Formula: see text] nm. Our study provides concise target residues and target binding energy reduction between S-proteins and receptors for the development of new therapeutics treatments for COVID-19 guided by computational design.