bims-antpol 2024-10-27 papers

Issue of 2024–10–27
three papers selected by
Rick Sheridan, EMSKE Phytochem

J Ethnopharmacol. 2024 Oct 19. pii: S0378-8741(24)01277-7. [Epub ahead of print] 118978

Combining virus-based affinity ultrafiltration method with serum pharmacochemistry to identify the antiviral pharmacodynamic substances in licorice.

Zhongyuan Li, Meiyue Dong, Zinuo Chen, Chengcheng Zhang, Jiayu Jiang, Miaomiao Liu, Qinghua Cui.

ETHNOPHARMACOLOGICAL RELEVANCE: Liorice (Glycyrrhiza uralensis Fisch.), a widely used Chinese herbal medicine, is frequently employed in clinical practice to treat viral pneumonia. However, the pharmacodynamic substances and mechanisms of action responsible for its antiviral effects against H1N1 and RSV remain unclear.
AIM OF THE STUDY: To investigate the antiviral effects of licorice against H1N1 and RSV. Building on this, we aimed to more comprehensively and accurately identify the pharmacodynamic substances in licorice responsible for its antiviral activity and mechanisms of action against these two viruses.
MATERIALS AND METHODS: Firstly, the antiviral effects of licorice against H1N1 and RSV were confirmed through in vivo and in vitro experiments. Then, a combination of virus-based affinity ultrafiltration method (VAUM) and serum pharmacochemistry were used to screen for pharmacological substances in licorice and identify their molecular targets against H1N1 and RSV.
RESULTS: The in vivo experiments showed that licorice effectively alleviates H1N1 and RSV induced weight loss and lung tissue damage in mice, while also reducing viral loads of H1N1 and RSV in the lungs. Subsequent in vitro experiments confirmed the presence of original compounds in licorice that directly inhibit H1N1 and RSV. By combining both methods, glycyrrhizic acid, glycyrrhetinic acid (GA), isoliquiritigenin (ISL), and glyasperin A (targeting the M2 ion channel) were ultimately identified as the pharmacodynamic substances in licorice responsible for anti-H1N1 activity. Additionally, licochalcone A (LCA) and glyasperin A, which target RSV surface proteins, were identified as the pharmacodynamic substances responsible for anti-RSV activity.
CONCLUSIONS: Traditional Chinese medicine (TCM) exerts its antiviral effects through a 'multi-component, multi-target' mechanism, which poses challenges for single active compound screening methods to adequately address. By integrating VAUM and serum pharmacochemistry for the first time, one approach focused on identifying compounds in TCM that directly bind to viral surface proteins, while the other targeted compounds that enter the bloodstream in their original form and exhibit antiviral activity. This provides a novel approach for studying the pharmacodynamic substances of antiviral effects in TCM.

Keywords: Antiviral; Licorice; Pharmacodynamic substances; Serum pharmacochemistry; Virus-based affinity ultrafiltration

DOI: https://doi.org/10.1016/j.jep.2024.118978

Microb Pathog. 2024 Oct 22. pii: S0882-4010(24)00542-4. [Epub ahead of print] 107075

Inhibitory activity of Euterpe oleracea Mart. fruit extract in West Nile virus infection.

Bruna N Teixeira, Fabiana P Albernaz, Andréa C Oliveira, Andre Marco O Gomes, Valéria L Carvalho, Carlos Alberto M Carvalho.

West Nile virus (WNV) is a neurovirulent arbovirus whose epidemic capacity is enhanced by the wide occurrence of competent vectors and susceptible avian amplifying hosts. In this study, we investigated the antiviral potential of Euterpe oleracea Mart. fruit extract (EoFE) in WNV infection of monkey kidney (Vero) cell cultures. A chromatographic authentication of the extract revealed a typical two-peak fingerprint attributable to the major anthocyanins of the fruit. As assessed by plaque assays in Vero cells, the extract showed a significant concentration-dependent antiviral effect when present throughout the infection procedure, reaching a maximum inhibition of 66.8% at 2 mg/mL without significant cytotoxicity or direct action on virus particles. A time-of-addition assay revealed that this anti-WNV effect was mostly exerted after virus entry, as incubation of Vero cells with EoFE before or during virus addition resulted in a nonsignificant decrease of infection efficiency. These results demonstrated a promising potential of EoFE in inhibiting WNV infection that can be further explored as an antiviral strategy.

Keywords: Antiviral activity; Euterpe oleracea Mart.; Orthoflavivirus; Vero cells; West Nile virus

DOI: https://doi.org/10.1016/j.micpath.2024.107075

J Ethnopharmacol. 2024 Oct 19. pii: S0378-8741(24)01274-1. [Epub ahead of print] 118975

The antiviral effect and potential mechanism of Houttuynia cordata Thunb. (HC) against coxsackievirus A4.

Qin Su, Hailin Wei, Yihan Xu, Yiliang Zhang, Wenlei Wang, Jiaxue Zhou, Sitong Liu, Xiaohui Yang, Le Zhou, Pinghu Zhang.

ETHNOPHARMACOLOGICAL RELEVANCE: Hand, foot, and mouth disease (HFMD) is mainly caused by various of enteroviruses such as enterovirus 71 (EVA71), coxsackievirus A16 (CVA16), CVA6, and CVA10 in infants and children under 5 years old. During the past 5 years, CVA4 has become the dominant pathogen resulting in HFMD in China. However, there are no effective vaccines and antiviral drugs available. Houttuynia cordata Thunb (HC). is a Chinese herbal medicine eaten as vegetables for treating viral infection diseases, but whether HC has anti-CVA4 effect remains unclear.
AIM OF THE STUDY: In this study, we want to investigate the antiviral activity of HC against CVA4 in vitro and in vivo and elucidate the potential mechanism of HC against CVA4.
MATERIALS AND METHODS: MTT assay were used to evaluate the cytotoxicity of HC. Virus titers assay, CPE assay, violet staining and immunofluorescence were used to investigate the antiviral effect of HC against CVA4. A 13-day-old suckling mice model was established to evaluate the therapeutic efficacy of HC against CVA4 infection. Western blot, qRT-PCR and time-of-drug addition assay were performed to elucidate the potential mechanism of HC against CVA4 infection.
RESULTS: MTT assay indicated the cytotoxicity concentration of HC on Vero cells and RD cells were more than 1mg/ml, suggesting that the low cytotoxicity of HC. In vitro antiviral assay revealed that HC could dose-dependently prevent the CPE, suppress the release of newborn virus, and inhibit the replication of CVA4 by decreasing viral RNA transcription and protein expression with IC50 of 88.96 μg/mL. A time-of-addition assay showed that HC mainly exerted anti-CVA4 effect by inhibiting virus replication at the post-entry stage. In vivo results further demonstrated that HC could effectively prevent the lethal infection of CVA4 by promoting survival, improving clinical symptoms, prolonging the survival time, inhibiting excessive inflammatory responses, and reducing pathological injury in vivo. Mechanistic studies revealed inhibition of p38 MAPK and JNK pathway over-activation may be the primary mechanism of HC against CVA4 infection.
CONCLUSION: In summary, our results for the first time demonstrated that HC not only effectively inhibited CVA4 replication, but also partially protected the lethal infection of CVA4 in vivo. Furthermore, pharmacological mechanism studies revealed that the primary mechanism of HC against CVA4 infection may be associated with its effect of inhibiting over-activation of p38 MAPK and JNK signaling pathways caused by enteroviruses. Our finding indicated that HC might be a potential innovative medicine for treating HFMD.

Keywords: CVA4; HFMD; Houttuynia cordata Thunb; MAPK

DOI: https://doi.org/10.1016/j.jep.2024.118975