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

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 a...

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Published inJournal of antibiotics Vol. 77; no. 2; pp. 85 - 92
Main Authors Yamasaki, Manabu, Sawa, Ryuichi, Muramatsu, Hideyuki, Yamamoto, Yui, Umekita, Maya, Kubota, Yumiko, Kanegae, Yumi, Igarashi, Masayuki
Format Journal Article
LanguageEnglish
Published Tokyo Springer Japan 01.02.2024
Springer Nature
Nature Publishing Group
Subjects
13/44
38/47
38/77
631/154
631/154/1435
Actinobacteria - genetics
Antibiotics
Antiviral agents
Antiviral Agents - pharmacology
Bacteriology
Biomedical and Life Sciences
Bioorganic Chemistry
Biotechnology & Applied Microbiology
Chromatography
DNA methylation
DNA, Viral - genetics
DNA, Viral - pharmacology
Fermentation
Genomes
Hep G2 Cells
Hepatitis
Hepatitis B
Hepatitis B virus
Humans
Immunology
Infections
Life Sciences
Life Sciences & Biomedicine
Medicinal Chemistry
Membrane permeability
Microbiology
Natural products
Organic Chemistry
Pharmacology
Pharmacology & Pharmacy
Science & Technology
Structural analysis
Viral infections
Virions
Virus Replication
FERMENTATION
WS75624-B
TAXONOMY
REPLICATION
SACCHAROTHRIX SP NO-75624
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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 EC 50 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.
AbstractList 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.
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 EC 50 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.
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 mu M 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.
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 EC 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.
Author Muramatsu, Hideyuki
Yamasaki, Manabu
Kanegae, Yumi
Igarashi, Masayuki
Sawa, Ryuichi
Umekita, Maya
Kubota, Yumiko
Yamamoto, Yui
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2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.
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Keywords FERMENTATION
WS75624-B
TAXONOMY
REPLICATION
SACCHAROTHRIX SP NO-75624
Language English
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Snippet Hepatitis B virus (HBV) causes chronic hepatitis in humans, and current antiviral therapies rarely treat viral infections. To improve the treatment efficacy,...
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pubmed
webofscience
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StartPage 85
SubjectTerms 13/44
38/47
38/77
631/154
631/154/1435
Actinobacteria - genetics
Antibiotics
Antiviral agents
Antiviral Agents - pharmacology
Bacteriology
Biomedical and Life Sciences
Bioorganic Chemistry
Biotechnology & Applied Microbiology
Chromatography
DNA methylation
DNA, Viral - genetics
DNA, Viral - pharmacology
Fermentation
Genomes
Hep G2 Cells
Hepatitis
Hepatitis B
Hepatitis B virus
Humans
Immunology
Infections
Life Sciences
Life Sciences & Biomedicine
Medicinal Chemistry
Membrane permeability
Microbiology
Natural products
Organic Chemistry
Pharmacology
Pharmacology & Pharmacy
Science & Technology
Structural analysis
Viral infections
Virions
Virus Replication
Title Catenulopyrizomicins, new anti-Hepatitis B virus compounds, from the rare actinomycete Catenuloplanes sp. MM782L-181F7
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