Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.09.289074v1?rss=1 Authors: Ortuso, F., Mercatelli, D., Guzzi, P. H., Giorgi, F. M. Abstract: SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these results with the current mutational status of these amino acids in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 10 distinct patients: N439K, G476S, S477N and N501Y. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V. Copy rights belong to original authors. Visit the link for more info