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Inhibitory effects of senkyuchachosan on SARS-CoV-2 papain-like protease activity in vitro

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Abstract

Papain-like protease (PLpro) enzyme plays a vital role in viral replication as it breaks down polyproteins and disrupts the host's immune response. There are few reports on Kampo formulas that focus on PLpro activity. In this study, we evaluated the inhibitory effects of senkyuchachosan, a traditional Japanese medicine, on PLpro of SARS-CoV-2, the virus responsible for causing COVID-19. We purified the PLpro enzyme and conducted in vitro enzymatic assays using specific substrates. Among the nine crude drugs present in senkyuchachosan, four (Cyperi Rhizoma, Schizonepetae Spica, Menthae Herba, and Camelliae sinensis Folium [CsF]) strongly inhibited PLpro activity. CsF, derived from Camellia sinensis (green tea), contains polyphenols, including catechins and tannins. To confirm that the PLpro inhibitory effects of senkyuchachosan predominantly stem from tannins, the tannins were removed from the decoction using polyvinylpolypyrrolidone (PVPP). The inhibitory effect of senkyuchachosan on PLpro activity was reduced by the removal of PVPP. In addition, the tannin fraction obtained from the CsF extracts showed significant PLpro inhibitory effects. These findings lay the groundwork for the potential development of therapeutic agents that target SARS-CoV-2 infection by intervening in proteolytic cleavage of the virus.

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Funding

This study was partially supported by JSPS KAKENHI (Grant numbers JP23K14372 to M. K. and JP22K06625 to T.H.).

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Authors and Affiliations

  1. School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado, Saitama, 350–0295, Japan

    Yuka Kiba, Takashi Tanikawa, Takami Yokogawa & Masashi Kitamura

  2. Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan

    Tsuyoshi Hayashi

  3. Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado, Saitama, 350-0295, Japan

    Aiko Sano & Ryuichiro Suzuki

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  1. Yuka Kiba
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  2. Takashi Tanikawa
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  3. Tsuyoshi Hayashi
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  4. Takami Yokogawa
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Correspondence to Masashi Kitamura.

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Kiba, Y., Tanikawa, T., Hayashi, T. et al. Inhibitory effects of senkyuchachosan on SARS-CoV-2 papain-like protease activity in vitro. J Nat Med 78, 784–791 (2024). https://doi.org/10.1007/s11418-024-01788-0

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