
Catenulopyrizomicins, new anti-hepatitis b virus compounds, from the rare actinomycete catenuloplanes sp. Mm782l-181f7
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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
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customer support SIMILAR CONTENT BEING VIEWED BY OTHERS EVALUATION OF A-AZEPANO-TRITERPENOIDS AND RELATED DERIVATIVES AS ANTIMICROBIAL AND ANTIVIRAL AGENTS Article 12 July 2021 AN
ANTI-INFLUENZA A VIRUS MICROBIAL METABOLITE ACTS BY DEGRADING VIRAL ENDONUCLEASE PA Article Open access 19 April 2022 A NOVEL PIPERAZINE DERIVATIVE THAT TARGETS HEPATITIS B SURFACE ANTIGEN
EFFECTIVELY INHIBITS TENOFOVIR RESISTANT HEPATITIS B VIRUS Article Open access 03 June 2021 REFERENCES * Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen
CJ, Taiwan Community-Based Cancer Screening Project Group 2002. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Eng J Med. 2002;347:168–74. Article CAS Google Scholar *
Durantel D, Zoulim F. New antiviral targets for innovative treatment concepts for hepatitis B virus and hepatitis delta virus. J Hepatol. 2016;64:S117–31. Article CAS PubMed Google
Scholar * Pei Y, Wang C, Yan SF, Liu G. Past, current, and future developments of therapeutic agents for treatment of chronic hepatitis B virus infection. J Med Chem. 2017;60:6461–79.
Article CAS PubMed Google Scholar * Beck J, Nassal M. Hepatitis B virus replication. World J Gastroenterol. 2007;13:48–64. Article CAS PubMed PubMed Central Google Scholar * Seeger
C, Mason WS. Molecular biology of hepatitis B virus infection. Virology. 2015;479-480:672–86. Article CAS PubMed Google Scholar * Suzuki M, Kondo S, Yamasaki M, Matsuda N, Nomoto A,
Suzuki T, Saito I, Kanegae Y. Efficient genome replication of hepatitis B virus using adenovirus vector: a compact pregenomic RNA-expression unit. Sci Rep. 2017;7:41851. Article CAS PubMed
PubMed Central Google Scholar * Takizawa N, Yamasaki M. Current landscape and future prospects of antiviral drugs derived from microbial products. J Antibiot. 2017;71:45–52. Article
Google Scholar * Yamasaki M, Matsuda N, Matoba K, Kondo S, Kanegae Y, Saito I, Nomoto A. Acetophenone 4-nitrophenylhydrazone inhibits Hepatitis B virus replication by modulating capsid
assembly. Virus Res. 2021;306:198565. Article CAS PubMed Google Scholar * Nishio M, Tomatsu K, Konishi M, Tomita K, Oki T, Kawaguchi H, Clardy J. Karnamicin, a complex of new antifungal
antibiotics. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties. J Antibiot. 1989;42:852–68. Article CAS Google Scholar * Urban M, McMillan DJ, Canning G,
Newell A, Brown E, Mills JS, Jupp R. In vitro activity of hepatitis B virus polymerase: requirement for distinct metal ions and the viral epsilon stem-loop. J Gen Virol. 1998;79:1121–31.
Article CAS PubMed Google Scholar * Toyoda T, Wang Y, Wen Y, Tanaka Y. Fluorescence-based biochemical analysis of human hepatitis B virus reverse transcriptase activity. Anal Biochem.
2020;597:113642. Article CAS PubMed Google Scholar * Chang LJ, Hirsch RC, Ganem D, Varmus HE. Effects of insertional and point mutations on the functions of the duck hepatitis B virus
polymerase. J Virol. 1990;64:5553–8. Article CAS PubMed PubMed Central Google Scholar * Wei X, Peterson DL. Expression, purification, and characterization of an active RNase H domain of
the hepatitis B viral polymerase. J Biol Chem. 1996;271:32617–22. Article CAS PubMed Google Scholar * Lu G, Lomonosova E, Cheng X, Moran EA, Meyers MJ, Le Grice SF, Thomas CJ, Jiang JK,
Meck C, Hirsch DR, D’Erasmo MP, Suyabatmaz DM, Murelli RP, Tavis JE. Hydroxylated tropolones inhibit hepatitis B virus replication by blocking viral ribonuclease H activity. Antimicrob
Agents Chemother. 2015;59:1070–9. Article PubMed PubMed Central Google Scholar * Jiang B, Hildt E. Intracellular trafficking of HBV particles. Cells. 2020;9:2023. Article CAS PubMed
PubMed Central Google Scholar * Lenhoff RJ, Summers J. Coordinate regulation of replication and virus assembly by the large envelope protein of an avian hepadnavirus. J Virol.
1994;68:4565–71. Article CAS PubMed PubMed Central Google Scholar * Ning X, Nguyen D, Mentzer L, Adams C, Lee H, Ashley R, Hafenstein S, Hu J. Secretion of genome-free hepatitis B virus
- single strand blocking model for virion morphogenesis of para-retrovirus. PLoS Pathog. 2011;7:e1002255. Article CAS PubMed PubMed Central Google Scholar * Bai L, Zhang X, Kozlowski
M, Li W, Wu M, Liu J, Chen L, Zhang J, Huang Y, Yuan Z. Extracellular hepatitis B Virus RNAs are heterogeneous in length and circulate as capsid-antibody complexes in addition to virions in
chronic hepatitis B patients. J Virol. 2018;92:e00798–18. Article CAS PubMed PubMed Central Google Scholar * Yu Z, Huang JP, Yang J, Liu C, Yan Y, Wang L, Zhao J, Chen Y, Xiang W, Huang
SX. Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors. Nat Commun. 2023;14:209. Article CAS PubMed PubMed Central Google Scholar * Tsurumi Y, Ueda
H, Hayashi K, Takase S, Nishikawa M, Kiyoto S, Okuhara M. WS75624 A and B, new endothelin converting enzyme inhibitors isolated from _Saccharothrix_ sp. No. 75624. I. Taxonomy, fermentation,
isolation, physico-chemical properties and biological activities. J Antibiot. 1995;48:1066–72. Article CAS Google Scholar * Yoshimura S, Tsurumi Y, Takase S, Okuhara M. WS75624 A and B,
new endothelin converting enzyme inhibitors isolated from _Saccharothrix_ sp. No. 75624. II. Structure elucidation of WS75624 A and B. J Antibiot. 1995;48:1073–5. Article CAS Google
Scholar * Kimura T, Inahashi Y, Matsuo H, Suga T, Iwatsuki M, Shiomi K, Takahashi Y, Ōmura S, Nakashima T. Pyrizomicin A and B: structure and bioactivity of new thiazolyl pyridines from
_Lechevalieria aerocolonigenes_ K10-0216. J Antibiot. 2018;71:606–8. Article CAS Google Scholar * Guo F, Zhao Q, Sheraz M, Cheng J, Qi Y, Su Q, Cuconati A, Wei L, Du Y, Li W, Chang J, Guo
JT. HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways. PLoS Pathog. 2017;13:e1006658. Article
PubMed PubMed Central Google Scholar Download references 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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *
Institute of Microbial Chemistry (BIKAKEN), Shinagawa-ku, Tokyo, Japan Manabu Yamasaki, Ryuichi Sawa, Hideyuki Muramatsu, Yui Yamamoto, Maya Umekita, Yumiko Kubota & Masayuki Igarashi *
Core Research Facilities of Basic Science, Research Center for Medical Science, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan Yumi Kanegae Authors * Manabu Yamasaki View
author publications You can also search for this author inPubMed Google Scholar * Ryuichi Sawa View author publications You can also search for this author inPubMed Google Scholar * Hideyuki
Muramatsu View author publications You can also search for this author inPubMed Google Scholar * Yui Yamamoto View author publications You can also search for this author inPubMed Google
Scholar * Maya Umekita View author publications You can also search for this author inPubMed Google Scholar * Yumiko Kubota View author publications You can also search for this author
inPubMed Google Scholar * Yumi Kanegae View author publications You can also search for this author inPubMed Google Scholar * Masayuki Igarashi View author publications You can also search
for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Manabu Yamasaki. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare no competing interests.
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law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 25 September 2023 * Revised: 31
October 2023 * Accepted: 01 November 2023 * Published: 27 November 2023 * Issue Date: February 2024 * DOI: https://doi.org/10.1038/s41429-023-00681-4 SHARE THIS ARTICLE Anyone you share the
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