Evaluation of antiviral activity of organic–polyoxometalate hybrids based on berberine against encephalomyocarditis virus in vitro

The clinical application of POM drugs is limited by their poor stability, nonspecific accumulation, and inevitable side effects on normal tissues. Recently, organic or biological groups were designed and linked covalently or non-covalently with POMs to regulate the biological performance of molecules and introduce another bioactivity into POMs.

Berberine (BR), a natural isoquinoline alkaloid from Coptis Chinensis herb, is frequently used as a treatment for bacterial diarrhea in clinical practice. Modern studies have found that BR not only possesses antibacterial and antiviral activities but also synergistic effects and enhanced efficacy when it is used in combination with other drugs. However, no clear research results or literature have reported the specific effects of POM, BR, or their combination on EMCV.

In our previous study, we synthesized BR-POMs and investigated their structures, aggregate morphologies, and antibacterial activities. In the present study, the organic–POM hybrids BR4[SiW₁₂O₄₀] (BR-SiW), BR₃[PMo₁₂O₄₀] (BR-PMo), BR₄K[EuSiW₁₁O₄₀]∙2H₂O (BR-EuSiW), and BR₆Na₃[EuW₁₀O₃₆] (BR-EuW) were fabricated using POMs and BR. The thermogravimetric results indicated that the hybrids had higher thermal stability than BR.

The four synthesized BR-POMs exhibited distinct antiviral effects. According to the MTT results, all four hybrids inhibited EMCV and PRV, with a stronger effect on EMCV. Among the hybrids, BR-EuSiW was further screened for its antiviral ability. The time-of-addition assay results demonstrate that the antiviral ability of BR-EuSiW is dose-dependent and may act on the virus at its biosynthesis stage to inhibit virus proliferation. These experimental data are helpful for the development of POM-based antiviral drugs against EMCV and demonstrate that the addition of traditional Chinese medicine monomer molecules can reduce the toxicity of POMs to BHK-21. Research on organic–POM hybrids remains scarce, and their clinical applications are even more unexplored. This new approach could open avenues for combining organic and inorganic antivirals, leveraging their synergistic potential to develop next-generation antiviral therapies. This work promotes the development of POM-based drugs for clinical application by controlling the organic cations on the surface of organic–POM hybrids, ultimately yielding new POM drugs with high efficiency and low toxicity.

This work was supported by Open Funds of the Biomedical Research Center from Northwest Minzu University (No. BRC-KF202303), Fundamental Research Funds for the Central Universities (No. 31920240105), and the National Natural Science Foundation of China (No. 32260037).

About the Authors

Dr. Chunxia Tan is an associate professor in Gansu University of Chinese Medicine, China. His research interests focus on the structural modification of natural products and their biological activities, as well as the preparation, characterization and antiviral research of organic-polyoxometalate complexes. Until now, he has published more than 20 papers in Acta Mater and other journals, presided over 5 provincial scientific research projects.

About the Journal

Polyoxometalates (ISSN 2957-9821) is a peer-reviewed (single-blind), open-access and interdisciplinary journal, sponsored by Tsinghua University. It publishes high-quality original research and authoritative reviews that focus on cutting-edge advancements in polyoxometalates, and clusters of metals, metal oxides and chalcogenides. Expeditious peer review enabling timely publication is a key feature of Polyoxometalates. It is indexed by ESCI, Scopus (CiteScore 2024 = 14.7), Ei Compendex, CAS, and DOAJ. For details about Polyoxometalates, please visit: https://www.sciopen.com/journal/2957-9821.