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Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7

The Journal of Antibiotics volume 77, pages 85–92 (2024)Cite this article

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Abstract

Hepatitis B virus (HBV) causes chronic hepatitis in humans, and current antiviral therapies rarely treat viral infections. To improve the treatment efficacy, novel therapeutic agents, especially those with different mechanisms of action, need to be developed for use in combination with the current antivirals. Here, we isolated new anti-HBV compounds, named catenulopyrizomicins A–C, from the fermentation broth of rare actinomycete Catenuloplanes sp. MM782L-181F7. Structural analysis revealed that these compounds contained a structure that is composed of thiazolyl pyridine moiety. The catenulopyrizomicins reduced the amount of intracellular viral DNA in HepG2.2.15 cells with EC50 values ranging from 1.94 to 2.63 µM with small but notable selectivity. Mechanistic studies indicated that catenulopyrizomicin promotes the release of immature virion particles that fail to be enveloped through alterations in membrane permeability.

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Acknowledgements

We thank Dr. Yasuhiro Takehana and Ms. Rie Arisaka for their technical assistance with isolating catenulopyrizomicins, and Dr. Kiyoko Iijima for the HRESI-MS and NMR measurements. We would like to thank Editage (www.editage.jp) for English language editing. This study is dedicated to the memory of Dr. Akio Nomoto, passed away in 2014, who inspired us a lot to find microbial compounds with antiviral activities. This study was supported by JSPS KAKENHI (grant number JP15K08507) and the Research Program on Hepatitis of the Japan Agency for Medical Research and Development (AMED) (grant number JP20fk0310102).

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Authors and Affiliations

  1. Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan

    Manabu Yamasaki, Ryuichi Sawa, Hideyuki Muramatsu, Yui Yamamoto, Maya Umekita, Yumiko Kubota & Masayuki Igarashi

  2. Core Research Facilities of Basic Science, Research Center for Medical Science, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan

    Yumi Kanegae

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  1. Manabu Yamasaki
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Correspondence to Manabu Yamasaki.

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Yamasaki, M., Sawa, R., Muramatsu, H. et al. Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7. J Antibiot 77, 85–92 (2024). https://doi.org/10.1038/s41429-023-00681-4

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