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

• Published in: Journal 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
• Language: English
• 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
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/s41429-023-00681-4

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.