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Thermodynamics of the Interaction Between SARS-CoV-2 Spike Protein and Human ACE2 Receptor. Effects of Possible Ligands

preprint
revised on 27.04.2020 and posted on 28.04.2020 by Cristina Garcia-Iriepa, Cecilia Hognon, Antonio Francés-Monerris, Isabel Iriepa, Tom Miclot, Giampaolo Barone, Antonio Monari, Marco Marazzi

Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.

History

Email Address of Submitting Author

antonio.monari@univ-lorraine.fr

Institution

Université de Lorraine - Nancy & CNRS

Country

France

ORCID For Submitting Author

0000-0001-9464-1463

Declaration of Conflict of Interest

No conflct of interest

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