Inhibitory effect of honokiol on furin-like activity and SARS-CoV-2 infection

https://doi.org/10.1016/j.jtcme.2021.09.005Get rights and content
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Abstract

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a pandemic and has caused damage to the lives of the people and economy of countries. However, the therapeutic reagents against SARS-CoV-2 remain unclear. The spike (S) protein of SARS-CoV-2 contains a cleavage motif at the S1/S2 boundary, known to be cleaved by furin. As cleavage is essential for S protein activation and viral entry, furin was selected as the target compound. In this study, we examined the inhibitory effects of two lignans (honokiol and magnolol) on furin-like enzymatic activity using a fluorogenic substrate with whole-cell lysates. Of two compounds tested, honokiol partially inhibited furin-like enzymatic activity. We further examined the anti-SARS-CoV-2 activity of honokiol using VeroE6 cell line, which is stably expressing a transmembrane protease serine 2 (TMPRSS2). It was shown that honokiol exhibited remarkable inhibition of SARS-CoV-2 infection. Therefore, honokiol and crude drugs which contain honokiol such as Magnolia species have a potential therapeutic reagents for SARS-CoV-2.

Keywords

SARS-CoV-2
Furin
COVID-19
Honokiol
Spike protein

Abbreviations

COVID-19
coronavirus disease 2019
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
TMPRSS2
transmembrane protease serine 2

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Peer review under responsibility of The Center for Food and Biomolecules, National Taiwan University.

1

These authors contributed equally to this study.