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

Takashi Tanikawa; Tsuyoshi Hayashi; Ryuichiro Suzuki; Masashi Kitamura; Yutaka Inoue

doi:10.1016/j.jtcme.2021.09.005

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

J Tradit Complement Med. 2022 Jan;12(1):69-72. doi: 10.1016/j.jtcme.2021.09.005. Epub 2021 Sep 16.

Authors

Takashi Tanikawa¹, Tsuyoshi Hayashi², Ryuichiro Suzuki³, Masashi Kitamura⁴, Yutaka Inoue¹

Affiliations

¹ Laboratory of Nutri-Pharmacotherapeutics Management, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan.
² Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
³ Laboratory of Natural Products & Phytochemistry, Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan.
⁴ Laboratory of Pharmacognocy, School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan.

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: COVID-19; COVID-19, coronavirus disease 2019; Furin; Honokiol; SARS-CoV-2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Spike protein; TMPRSS2, transmembrane protease serine 2.