Invalidation of geraniin as a potential inhibitor against SARS-CoV-2 main protease

Abstract

Recently, geraniin has been identified as a potent antiviral agent targeting SARS-CoV-2 main protease (Mpro). Considering the potential of geraniin in COVID-19 treatment, a stringent validation for its Mpro inhibition is necessary. Herein, we rigorously evaluated the in vitro inhibitory effect of geraniin on Mpro using the fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), and dimerization-dependent red fluorescent protein (ddRFP) assays. Our data indicate that geraniin is not a potential inhibitor against Mpro based on the results from a set of in vitro assays. These results suggest a stringent in vitro validation with diverse biochemical assays is essential for the discovery of Mpro inhibitors, and the fluorescence quenching effect caused by natural products should be considered when evaluating Mpro inhibitors.

GRAPHICAL ABSTRACT

Keywords:

• SARS-CoV-2
• main protease inhibitor
• geraniin
• fluorescence polarization
• fluorescence quenching effect

Acknowledgments

The authors thank Prof. Yanchang Wang (Department of Biomedical Sciences, College of Medicine, Florida State University, USA) for his insightful comments of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Natural Science Foundation of Anhui Province, China (No. 1808085QH265); University Natural Science Research Project of Anhui Province, China (No. KJ2021A0839); and Postgraduate Academic Innovation Program of Anhui Province, China (No. 2022xscx129).