Evaluation of natural products from virtual screenings as SARS-CoV-2 main protease inhibitors using combinational experiments

Abstract

Recently, andrographolide, kaempferol, maslinic acid, rutin, and schaftoside have been identified as potent SARS-CoV-2 main protease (Mpro) inhibitors via molecular docking studies. However, no comprehensive in vitro testing of these compounds against Mpro has been conducted. In this study, we rigorously evaluated the in vitro inhibition of Mpro by these compounds using combinational experiments, including fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data revealed that these compounds are not Mpro inhibitors based on the results from a set of in vitro assays. These results suggest that an efficient combination of a molecular docking approach and an experimental assay is essential for the discovery of Mpro inhibitors in the future.

Graphical Abstract

Keywords:

• SARS-CoV-2
• main protease inhibitor
• fluorescence polarization
• andrographolide
• schaftoside

Acknowledgments

The authors thank Prof. Yanchang Wang (College of Medicine, Florida State University, Tallahassee, USA) for his helpful readings of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Postgraduate Academic Innovation Program of Anhui Province, China [2022xscx129], University Natural Science Research Project of Anhui Province, China [KJ2021A0839]; The Young Fellow Program of Wannan Medical College, China [wyqnyx202104].