Related Experiment Video
Updated: Aug 13, 2026
A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation
Published on: January 9, 2019
Virtual screening and in vitro validation of natural compound inhibitors against SARS-CoV-2 spike protein
Helen Power1, Jiadai Wu2, Stuart Turville3
1School of Chemical and Biomolecular Engineering, Faculty of Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Advanced Food Engineering, The University of Sydney, Sydney, NSW 2006, Australia; Bioengineering and Molecular Medicine Laboratory, The Children's Hospital at Westmead and Westmead Institute for Medical Research, Westmead, NSW 2145, Australia.
Abstract:
The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a major public health burden and has resulted in millions of deaths worldwide. As effective treatments are limited, there is a significant requirement for high-throughput, low resource methods for the discovery of novel antivirals. The SARS-CoV-2 spike protein plays a key role in viral entry and has been identified as a therapeutic target. Using the available spike crystal structure, we performed a virtual screen with a library of 527 209 natural compounds against the receptor binding domain of this protein. Top hits from this screen were subjected to a second, more comprehensive molecular docking experiment and filtered for favourable ADMET properties. The in vitro activity of 10 highly ranked compounds was assessed using a virus neutralisation assay designed to facilitate viral entry in a physiologically relevant manner via the plasma membrane route. Subsequently, four compounds ZINC02111387, ZINC02122196, SN00074072 and ZINC04090608 were identified to possess antiviral activity in the µM range. These findings validate the virtual screening method as a tool for identifying novel antivirals and provide a basis for future drug development against SARS-CoV-2.
