Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

6533b7d7fe1ef96bd1269044

RESEARCH PRODUCT

Targeting SARS-CoV-2 RBD Interface: a Supervised Computational Data-Driven Approach to Identify Potential Modulators

Maria Rita Gulotta Nedra Mekni Alessandro Padova Giada De Simone Ugo Perricone Maria Cristina De Rosa Jessica Lombino Patrizia Diana

subject

Protein domain Pneumonia Viral Druggability Drug Evaluation Preclinical protein-protein interactions Computational biology Biology Molecular Dynamics Simulation Peptidyl-Dipeptidase A Molecular dynamics 01 natural sciences Biochemistry Molecular Docking Simulation Antiviral Agents dockingmolecular dynamic Protein–protein interaction Small Molecule Libraries Betacoronavirus Protein Domains Drug Discovery Humans General Pharmacology Toxicology and Pharmaceutics Pandemics Pharmacology Full Paper pharmacophore 010405 organic chemistry Drug discovery SARS-CoV-2 Organic Chemistry COVID-19 Small molecule 0104 chemical sciences Protein-Protein Interaction Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Docking (molecular)Spike Glycoprotein Coronavirus docking Molecular Medicine Angiotensin-Converting Enzyme 2 Pharmacophore Coronavirus Infections Protein Binding

description

Coronavirus disease 2019 (COVID-19) has spread out as a pandemic threat affecting over 2 million people. The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. Herein, we present a computational study aimed at identifying small molecules potentially able to target RBD. Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV-2 RBD and ACE2 PD might be prone to small molecule modulation, due to the hydrophilic nature of the bi-molecular recognition process and the presence of druggable hot spots. The fundamental objective is to identify, and provide to the international scientific community, hit molecules potentially suitable to enter the drug discovery process, preclinical validation and development. © 2020 Wiley-VCH GmbH

year	journal	country	edition	language
2020-09-04

http://hdl.handle.net/10447/454883