Phloroglucinol Oligomers from Callistemon rigidus as Novel Anti-Hantavirus Replication Agents

TL;DR

Scientists found new plant compounds from Callistemon rigidus that effectively block hantavirus replication, offering potential treatments for a disease with no approved drugs.

Contribution

The discovery of two new phloroglucinol trimers with superior anti-hantavirus activity compared to ribavirin.

Findings

Callistemontrimer A showed higher anti-HTNV activity than ribavirin.

Callistemontrimer A inhibits viral replication by interacting with HTNV's RNA-dependent RNA polymerase.

Oligomeric phloroglucinols are promising candidates for anti-hantavirus therapeutics.

Abstract

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 Callistemon rigidus 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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