A novel screening strategy of anti-SARS-CoV-2 drugs via blocking interaction between Spike RBD and ACE2

[Display omitted] •Drug property and binding energy were negative correlation for compounds.•8 kinds of common structures with high anti-SARS-CoV-2 activity were selected.•The structure-activity relationship between drugs and SARS-CoV-2 therapy was built.•This is the first study on screening strategy of anti-SARS-CoV-2 drugs. Corona virus disease 2019 has spread worldwide, and appropriate drug design and screening activities are required to overcome the associated pandemic. Using computational simulation, blockade mechanism of SARS-CoV-2 spike receptor binding domain (S RBD) and human angiotensin converting enzyme 2 (hACE2) was clarified based on interactions between RBD and hesperidin. Interactions between anti-SARS-CoV-2 drugs and therapy were investigated based on the binding energy and druggability of the compounds, and they exhibited negative correlations; the compounds were classified into eight common types of structures with highest activity. An anti-SARS-CoV-2 drug screening strategy based on blocking S RBD/hACE2 binding was established according to the first key change (interactions between hesperidin and S RBD/hACE2) vs the second key change (interactions between anti-SARS-CoV-2 drugs and RBD/hACE2) trends. Our findings provide valuable information on the mechanism of RBD/hACE2 binding and on the associated screening strategies for anti-SARS-CoV-2 drugs based on blocking mechanisms of pockets.