Punicalagin inhibits Getah virus replication by directly blocking viral attachment and internalization

Published: 6 September 2026| Version 1 | DOI: 10.17632/3rptcr8rxj.1
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Description

Getah virus (GETV) is an important mosquito-borne zoonotic pathogen, like Chikungunya virus (CHIKV), belonging to the genus Alphavirus of the family Togaviridae. Since 2024, the highly virulent GETV GIII variant strain has emerged in China, causing severe abortions in sows and piglet mortality rates as high as 80%, resulting in substantial economic losses to the swine industry. However, no approved vaccines or effective antiviral drugs are currently available for the prevention and control of GETV. In this study, we screened a library of 113 natural compounds using a GETV-GFP reporter strain and identified 14 candidate molecules with anti-GETV activity. Among them, punicalagin (PUN) showed the most potent antiviral activity. In vitro experiments demonstrated that PUN exhibited significant dose-dependent inhibitory effects against multiple GETV strains, including the GETV-GFP strain, the highly virulent GIII variant strain HeN01 and the non-variant GIII strain HNny25. Mechanistic studies revealed that PUN blocks the viral attachment and internalization stages to exert its antiviral action. In addition, we found that PUN significantly inhibited the replication of other enveloped viruses, including porcine epidemic diarrhea virus (PEDV), pseudorabies virus (PRV), and vesicular stomatitis virus (VSV), but showed no activity against the non-enveloped virus Senecavirus A (SVA). Furthermore, in suckling mice challenged with the highly virulent HeN01 strain, PUN treatment significantly increased the survival rate to 66.7% (4/6), ameliorated growth and development indicators, and effectively reduced the viral load in major target organs. These findings not only provide a solid theoretical basis for the future clinical translation of PUN but also hold great promise in bridging the gap in specific GETV therapeutics.

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Steps to reproduce

First, using the GETV strain expressing green fluorescent protein, we screened a library of natural small-molecule compounds and identified punicalagin (PUN) with significant anti-GETV activity. Subsequently, the antiviral activity of PUN against different GETV strains was systematically evaluated through TCID50, immunofluorescence analysis (IFA), and RT-qPCR assays. Furthermore, the mechanism by which PUN inhibits GETV was explored through experiments on viral attachment, internalization, replication, release, and direct inactivation. Finally, the therapeutic effect of PUN was validated in vivo using a suckling mouse model infected with GETV.

Institutions

Categories

Virus, Antivirus Agent

Funders

  • National Natural Science Foundation of China
    Beijing, Beijing
    Grant ID: No. 32573409 and No. 32503038
  • Henan Natural Science Foundation
    Grant ID: No. 252300423606
  • Henan Provincial Joint Fund for Science and Technology Research and Development
    Grant ID: No. 252301420118
  • ‌Henan Provincial Science and Technology Tackling Key Problems Program
    Grant ID: No. 262102110046

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