RT Journal Article SR Electronic T1 Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.04.976027 DO 10.1101/2020.03.04.976027 A1 Houcemeddine Othman A1 Zied Bouslama A1 Jean-Tristan Brandenburg A1 Jorge da Rocha A1 Yosr Hamdi A1 Kais Ghedira A1 Najet-Srairi Abid A1 Scott Hazelhurst YR 2020 UL http://biorxiv.org/content/early/2020/03/27/2020.03.04.976027.abstract AB The spread of the COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor via which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with the phylogeny analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than mutation accumulation. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to hACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of human engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.