Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in hum...

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Main Authors: Jin-Xuan Yang, E-E Luo, Yue-Chun Wu, Kai Zhao, Wei Hou, Mu-Yuan Yu, Xu-Jie Qin, Xing-Lou Yang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/7/916
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author Jin-Xuan Yang
E-E Luo
Yue-Chun Wu
Kai Zhao
Wei Hou
Mu-Yuan Yu
Xu-Jie Qin
Xing-Lou Yang
author_facet Jin-Xuan Yang
E-E Luo
Yue-Chun Wu
Kai Zhao
Wei Hou
Mu-Yuan Yu
Xu-Jie Qin
Xing-Lou Yang
author_sort Jin-Xuan Yang
collection DOAJ
description Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from <i>Callistemon rigidus</i> leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics.
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spelling doaj-art-b5a531b612344979948676fc8c80ddfe2025-08-20T03:56:49ZengMDPI AGViruses1999-49152025-06-0117791610.3390/v17070916Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication AgentsJin-Xuan Yang0E-E Luo1Yue-Chun Wu2Kai Zhao3Wei Hou4Mu-Yuan Yu5Xu-Jie Qin6Xing-Lou Yang7Key Laboratory of Genetic Evolution & Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, ChinaState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaKey Laboratory of Genetic Evolution & Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, ChinaKey Laboratory of Genetic Evolution & Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, ChinaState Key Laboratory of Virology, Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, ChinaState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaState Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, ChinaKey Laboratory of Genetic Evolution & Animal Models, Yunnan International Joint Laboratory of Zoonotic Viruses, Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, ChinaZoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from <i>Callistemon rigidus</i> leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics.https://www.mdpi.com/1999-4915/17/7/916<i>Callistemon rigidus</i>phloroglucinol oligomershantavirusanti-HTNV activitymolecular docking
spellingShingle Jin-Xuan Yang
E-E Luo
Yue-Chun Wu
Kai Zhao
Wei Hou
Mu-Yuan Yu
Xu-Jie Qin
Xing-Lou Yang
Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
Viruses
<i>Callistemon rigidus</i>
phloroglucinol oligomers
hantavirus
anti-HTNV activity
molecular docking
title Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
title_full Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
title_fullStr Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
title_full_unstemmed Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
title_short Phloroglucinol Oligomers from <i>Callistemon rigidus</i> as Novel Anti-Hantavirus Replication Agents
title_sort phloroglucinol oligomers from i callistemon rigidus i as novel anti hantavirus replication agents
topic <i>Callistemon rigidus</i>
phloroglucinol oligomers
hantavirus
anti-HTNV activity
molecular docking
url https://www.mdpi.com/1999-4915/17/7/916
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