关键词: COVID-19 Co-infections Influenza virus Innate immunity Nutraceutical formula Polyphosphates SARS-CoV-2 Sincytial respiratory virus

Mesh : Humans Immunity, Innate / drug effects Antiviral Agents / pharmacology COVID-19 / immunology virology SARS-CoV-2 / drug effects immunology Anti-Infective Agents / pharmacology Polyphenols / pharmacology Dietary Supplements

来  源:   DOI:10.1186/s12967-024-05378-2   PDF(Pubmed)

Abstract:
BACKGROUND: The innate immunity acts during the early phases of infection and its failure in response to a multilayer network of co-infections is cause of immune system dysregulation. Epidemiological SARS-CoV-2 infections data, show that Influenza Virus (FLU-A-B-C) and Respiratory Syncytial Virus (RSV) are co-habiting those respiratory traits. These viruses, especially in children (mostly affected by \'multi-system inflammatory syndrome in children\' [MIS-C] and the winter pandemic FLU), in the aged population, and in \'fragile\' patients are causing alteration in immune response. Then, bacterial and fungal pathogens are also co-habiting the upper respiratory traits (e.g., Staphylococcus aureus and Candida albicans), thus contributing to morbidity in those COVID-19 affected patients.
METHODS: Liquid chromatography coupled with high-resolution mass spectrometry using the quadrupole orbital ion trap analyser (i.e., UHPLC-Q-Orbitrap HRMS) was adopted to measure the polyphenols content of a new nutraceutical formula (Solution-3). Viral infections with SARS-CoV-2 (EG.5), FLU-A and RSV-A viruses (as performed in BLS3 authorised laboratory) and real time RT-PCR (qPCR) assay were used to test the antiviral action of the nutraceutical formula. Dilution susceptibility tests have been used to estimate the minimum inhibitory and bactericidal concentration (MIC and MBC, respectively) of Solution-3 on a variety of microorganisms belonging to Gram positive/ negative bacteria and fungi. Transcriptomic data analyses and functional genomics (i.e., RNAseq and data mining), coupled to qPCR and ELISA assays have been used to investigate the mechanisms of action of the nutraceutical formula on those processes involved in innate immune response.
RESULTS: Here, we have tested the combination of natural products containing higher amounts of polyphenols (i.e., propolis, Verbascum thapsus L., and Thymus vulgaris L.), together with the inorganic long chain polyphosphates \'polyPs\' with antiviral, antibacterial, and antifungal behaviours, against SARS-CoV-2, FLU-A, RSV-A, Gram positive/ negative bacteria and fungi (i.e., Candida albicans). These components synergistically exert an immunomodulatory action by enhancing those processes involved in innate immune response (e.g., cytokines: IFNγ, TNFα, IL-10, IL-6/12; chemokines: CXCL1; antimicrobial peptides: HBD-2, LL-37; complement system: C3).
CONCLUSIONS: The prophylactic antimicrobial success of this nutraceutical formula against SARS-CoV-2, FLU-A and RSV-A viruses, together with the common bacteria and fungi co-infections as present in human oral cavity, is expected to be valuable.
摘要:
背景:先天免疫在感染的早期起作用,其对多层共感染网络的反应失败是免疫系统失调的原因。流行病学SARS-CoV-2感染数据,表明流感病毒(FLU-A-B-C)和呼吸道合胞病毒(RSV)共同存在这些呼吸道性状。这些病毒,尤其是在儿童中(主要受“儿童多系统炎症综合征”[MIS-C]和冬季流感大流行影响),在老年人口中,在“脆弱的”患者中,免疫反应正在发生变化。然后,细菌和真菌病原体也共同存在上呼吸道特征(例如,金黄色葡萄球菌和白色念珠菌),从而导致那些受COVID-19影响的患者的发病率。
方法:使用四极轨道离子阱分析仪的液相色谱与高分辨率质谱联用(即,UHPLC-Q-OrbitrapHRMS)用于测量新的营养配方(Solution-3)的多酚含量。SARS-CoV-2(EG.5)病毒感染,使用FLU-A和RSV-A病毒(在BLS3授权实验室中进行)和实时RT-PCR(qPCR)测定来测试营养配方的抗病毒作用。稀释敏感性试验已用于估计最小抑制和杀菌浓度(MIC和MBC,分别)对属于革兰氏阳性/阴性细菌和真菌的各种微生物的溶液-3。转录组数据分析和功能基因组学(即,RNAseq和数据挖掘),与qPCR和ELISA测定相结合,已用于研究营养配方对先天免疫应答过程的作用机制。
结果:这里,我们已经测试了含有较高量多酚的天然产物的组合(即,蜂胶,VerbascumthapsusL.,和胸腺寻常L.),连同具有抗病毒作用的无机长链多磷酸盐,抗菌,和抗真菌行为,对抗SARS-CoV-2,FLU-A,RSV-A,革兰氏阳性/阴性细菌和真菌(即,白色念珠菌)。这些组分通过增强参与先天免疫应答的那些过程协同发挥免疫调节作用(例如,细胞因子:IFNγ,TNFα,IL-10,IL-6/12;趋化因子:CXCL1;抗微生物肽:HBD-2,LL-37;补体系统:C3)。
结论:该营养食品配方对SARS-CoV-2,FLU-A和RSV-A病毒的预防性抗菌成功,以及人类口腔中常见的细菌和真菌共感染,预计是有价值的。
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