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产气荚膜梭菌唾液酸酶作为新型抗禽流感H5N1感染药物在BALB/c小鼠中的应用潜力

Potential of Clostridium perfringens sialidase as a novel antiviral agent against avian influenza H5N1 infection in BALB/c mice.

作者信息

Silaen Otto Sahat Martua, Widyaningtyas Silvia Tri, Nugroho Christian Marco Hadi, Kurnia Ryan Septa, Putra Muhammad Ade, Indrawati Agustin, Krisnamurti Desak Gede Budi, Soebandrio Amin

机构信息

Doctoral Program in Biomedical Science, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia; Animal Health Diagnostic Unit, PT Medika Satwa Laboratoris, Bogor, Indonesia.

Virology and Cancer Pathobiology Research Centre, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia.

出版信息

Comp Immunol Microbiol Infect Dis. 2025 Aug;121:102373. doi: 10.1016/j.cimid.2025.102373. Epub 2025 Jun 26.

Abstract

The public health concern about H5N1 avian influenza persists because of its lethal nature and its capability to spread between different species and its growing resistance to conventional antiviral medications. The antiviral drug potential of sialidases from Clostridium perfringens remains under investigation because these enzymes can strip sialic acid from viral surfaces which prevents viral attachment to host cells. This study aimed to determine the antiviral effects of C. perfringens sialidase on H5N1-infected BALB/c mice through both preventive and curative treatment protocols. The mice received intranasal sialidase at two concentrations of 187.5 mU/ml and 375 mU/ml for three consecutive days either before viral exposure or after viral challenge. The study included weight tracking and ELISA tests to measure lung tissue viral antigens as well as lung tissue histopathology and IL-6 and TNF-α expression analysis. The treatment with 375 mU/ml sialidase twice proved most effective in maintaining physiological function and reducing viral load and lung tissue damage. The treatment results demonstrated that it reduced inflammatory response by lowering IL-6 and TNF-α expression levels. The research proves that C. perfringens sialidase exhibits antiviral and immunomodulatory actions when used in vivo. The curative outcome depends heavily on treatment dose and frequency which will impact future implementation. The antiviral properties of C. perfringens sialidase make it a promising therapeutic option for treating influenza virus strains that are resistant to drugs.

摘要

由于H5N1禽流感具有致命性、能够在不同物种间传播且对传统抗病毒药物的耐药性不断增强,因此公共卫生领域对其的担忧一直存在。产气荚膜梭菌唾液酸酶的抗病毒潜力仍在研究中,因为这些酶可以从病毒表面去除唾液酸,从而阻止病毒附着于宿主细胞。本研究旨在通过预防和治疗方案来确定产气荚膜梭菌唾液酸酶对感染H5N1的BALB/c小鼠的抗病毒效果。在病毒暴露前或病毒攻击后,小鼠连续三天接受两种浓度(187.5 mU/ml和375 mU/ml)的鼻内唾液酸酶给药。该研究包括体重跟踪、ELISA测试以测量肺组织病毒抗原,以及肺组织病理检查和IL-6和TNF-α表达分析。结果表明,375 mU/ml唾液酸酶两次给药在维持生理功能、降低病毒载量和肺组织损伤方面最为有效。治疗结果表明,它通过降低IL-6和TNF-α表达水平来减轻炎症反应。该研究证明,产气荚膜梭菌唾液酸酶在体内使用时具有抗病毒和免疫调节作用。治疗效果在很大程度上取决于治疗剂量和频率,这将影响未来的应用。产气荚膜梭菌唾液酸酶的抗病毒特性使其成为治疗耐药流感病毒株的有前景的治疗选择。

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