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一种新型载姜黄素的薄膜喷雾能抑制 SARS-CoV-2 和流感病毒感染并增强黏膜免疫。

A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity.

机构信息

Faculty of Dentistry, Thammasat University, Pathum Thani, Thailand.

Center for Research Innovation and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.

出版信息

Virol J. 2024 Jan 23;21(1):26. doi: 10.1186/s12985-023-02282-x.

DOI:10.1186/s12985-023-02282-x
PMID:38263162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10807123/
Abstract

BACKGROUND

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of bioactive compounds to be used as preventive measures for both inhibiting the virus binding and enhancing mucosal innate immunity. Curcumin has been shown to possess antiviral activity and modulate innate immunity. Therefore, the purpose of this study was to develop an oro-nasal film spray containing curcumin and determine its antiviral activity against SARS-CoV-2 and influenza virus infection, as well as its effects on mucosal innate immunity and inflammatory cytokines in vitro.

METHODS

The antiviral activity of the film spray against SARS-CoV-2, influenza A/H1N1, A/H3N2, and influenza B was assessed in vitro by plaque reduction assay. Cytotoxicity of the film spray to oral keratinocytes and nasal epithelial cells was assessed by MTT assay, and cytotoxicity to Vero and MDCK cells was assessed by an MTS-based cytotoxicity assay. Oral and nasal innate immune markers in response to the film spray were determined by ELISA and by a commercial Milliplex Map Kit, respectively.

RESULTS

Our data show that the film spray containing curcumin can inhibit both SARS-CoV-2 and influenza virus infections while maintaining cell viability. Results obtained among 4 viruses revealed that curcumin film spray demonstrated the highest inhibitory activity against SARS-CoV-2 with the lowest EC of 3.15 µg/ml and the highest SI value of 4.62, followed by influenza B (EC = 6.32 µg/ml, SI = 2.04), influenza A/H1N1 (EC = 7.24 µg/ml, SI = 1.78), and influenza A/H3N2 (EC > 12.5 µg/ml, SI < 1.03), respectively. Antimicrobial peptides LL-37 and HD-5, IL-6 and TNF-α produced by oral keratinocytes were significantly induced by the film spray, while hBD2 was significantly reduced.

CONCLUSION

Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.

摘要

背景

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)和流感病毒的感染仍然是全球主要的健康关注点。植物是生物活性化合物的良好来源,可作为预防措施,既能抑制病毒结合,又能增强黏膜固有免疫。姜黄素已被证明具有抗病毒活性和调节固有免疫的作用。因此,本研究旨在开发一种含有姜黄素的口腔-鼻腔喷雾,并确定其对 SARS-CoV-2 和流感病毒感染的抗病毒活性,以及对体外黏膜固有免疫和炎症细胞因子的影响。

方法

通过蚀斑减少法评估喷雾对 SARS-CoV-2、流感 A/H1N1、A/H3N2 和 B 型病毒的抗病毒活性。通过 MTT 测定法评估喷雾对口腔角质形成细胞和鼻腔上皮细胞的细胞毒性,通过 MTS 基于细胞毒性测定法评估对 Vero 和 MDCK 细胞的细胞毒性。通过 ELISA 和商业 Milliplex Map 试剂盒分别测定口腔和鼻腔固有免疫标志物对喷雾的反应。

结果

我们的数据表明,含有姜黄素的喷雾可以抑制 SARS-CoV-2 和流感病毒的感染,同时保持细胞活力。在 4 种病毒中获得的结果表明,姜黄素喷雾对 SARS-CoV-2 的抑制活性最高,EC 为 3.15μg/ml,SI 值为 4.62,其次是流感 B(EC=6.32μg/ml,SI=2.04),流感 A/H1N1(EC=7.24μg/ml,SI=1.78),和流感 A/H3N2(EC>12.5μg/ml,SI<1.03)。口腔角质形成细胞产生的抗菌肽 LL-37 和 HD-5、IL-6 和 TNF-α 明显受喷雾刺激,而 hBD2 则明显减少。

结论

含有姜黄素的喷雾通过抑制靶细胞中的 ACE-2 结合和增强黏膜固有免疫,对 SARS-CoV-2 感染具有多种作用。该喷雾还能抑制流感病毒感染。因此,姜黄素喷雾可能对预防 SARS-CoV-2 和流感的病毒感染有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/ed59ca1c71da/12985_2023_2282_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/ed59ca1c71da/12985_2023_2282_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/c87a192a69be/12985_2023_2282_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/6e35738aa554/12985_2023_2282_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/4f36b4ecbb2c/12985_2023_2282_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/29491f141189/12985_2023_2282_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/4dd62e2c3196/12985_2023_2282_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9899/10807123/ed59ca1c71da/12985_2023_2282_Fig8_HTML.jpg

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