Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays
Fulvio Perrella,
Federico Coppola,
Alessio Petrone,
Chiara Platella,
Daniela Montesarchio,
Annarita Stringaro,
Giampietro Ravagnan,
Maria Pia Fuggetta,
Nadia Rega,
Domenica Musumeci
Affiliations
Fulvio Perrella
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Federico Coppola
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Alessio Petrone
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Chiara Platella
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Daniela Montesarchio
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Annarita Stringaro
National Center for Drug Research and Evaluation, Italian National Institute of Health, 00161 Rome, Italy
Giampietro Ravagnan
Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche, 00133 Rome, Italy
Maria Pia Fuggetta
Institute of Translational Pharmacology, Consiglio Nazionale delle Ricerche, 00133 Rome, Italy
Nadia Rega
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
Domenica Musumeci
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy
In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)—two natural stilbene polyphenols with manifold, well known biological activities—with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.
