Wild-type SARS-CoV-2–ACE2 binding inhibitory activity of Zingiberaceae herbs and spices

Abstract

COVID-19 is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late December 2019. The present study assessed the potential of herbs and spices from the Zingiberaceae family to inhibit binding of the wild-type SAR-CoV-2 spike protein to human angiotensin-converting enzyme 2 (ACE2) using an in vitro binding inhibition assay. From the 21 assessed Zingiberaceae extracts, 10 significantly inhibited binding at 200 µg/mL. The binding inhibitory potential of the extracts did not correlate directly with total phenolic and flavonoid content, but rather with specific phytochemicals (active compounds). Among the tested extracts, B. rotunda extracts from three different sources exhibited significant inhibitory activity (42%–46% non-inhibition). Panduratin A (identified compound) and 4-hydroxypanduratin A (tentatively identified compound) were identified as active compounds responsible for the binding inhibitory activity in B. rotunda extracts. The inhibitory dose-response curve for binding inhibition was obtained for panduratin A, yielding an IC₅₀ of 0.38 µg/mL. Overall, Zingiberaceae plants, especially A. biflorum, B. rotunda, C. aromatic, C. mangga, C. zedoaria, K. parviflora, Kaempferia sp., and Z. montanum, exhibited potent binding inhibitory activity against wild-type SARS-CoV-2 cellular entry. Although this finding indicates the potential of Zingiberaceae plants as anti-SAR-CoV-2 agents, further research is needed, as the present study was limited to a biochemical assay using the wild-type spike protein. Thus, further validation using clinically relevant SARS-CoV-2 variants, cell-based viral infection models, and in vivo studies is required before antiviral efficacy can be concluded.

Keywords

bioactive compound / Coronavirus / COVID-19 / Panduratin A / SAR-CoV-2 cellular entry

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