Purpose: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection has grown into a pandemic and without a specific cure, disease management is the need of the hour through symptomatic interventions. Studies with severe acute respiratory syndrome-coronavirus (SARS-CoV) have highlighted the role of herbal medicines either in combination with antiviral drugs or by themselves in curtailing the severity of infection and associated inflammation. Divya-Swasari-Vati is an Indian ayurvedic formulation used in the treatment of chronic cough and lung inflammation, which is one of the first symptoms of SARS-CoV-2 infections.
Methods: In this study, we used a A549 cell xenotransplant in the swim bladder of zebrafish and modeled the SARS-CoV-2 infection by injecting the fish with a recombinant spike protein. The different groups were given normal feed or feed mixed with either dexamethasone (as the control drug) or Divya-Swasari-Vati. The changes in behavioral fever, infiltration of pro-inflammatory cells in the swim bladder, degeneration or presence of necrotic cells in the kidney, and gene expression of pro-inflammatory cytokines were studied to determine the rescue of the diseased phenotype.
Results: Challenge with the spike protein caused changes in the swim bladder cytology with infiltrating pro-inflammatory cells, skin hemorrhage, and increase in behavioral fever. This was also accompanied by increased mortality of the disease control fish. Treatment with Divya-Swasari-Vati reversed most of the disease symptoms including damage to the kidney glomerulocytes, and complete reversal of behavioral fever. Dexamethasone, used as a comparator, was only able to partly rescue the behavioral fever phenotype. Divya-Swasari-Vati also suppressed the pro-inflammatory cytokines, IL-6 and TNF-α, levels in a dose-dependent manner, under in vivo and in vitro conditions.
Conclusion: The study showed that the A549 xenotransplanted zebrafish injected with the recombinant spike protein of SARS-CoV-2 is an efficient model for the disease; and treatment with Divya-Swasari-Vati medicine rescued most of the inflammatory damage caused by the viral spike protein while increasing survival of the experimental fish.

Keywords: zebrafish, A549 xenotransplant, SARS-CoV-2 infection model, herbal medicines, ayurveda, Divya-Swasari-Vati, behavioral fever, cytokine profile


中文翻译：

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Calcio-Herbal Medicine Divya-Swasari-Vati 通过调节 IL-6 和 TNF-α 细胞因子改善人源化斑马鱼模型中 SARS-CoV-2 刺突蛋白诱导的病理特征和炎症

目的：严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染已发展为大流行病，在没有具体治愈方法的情况下，需要通过对症干预进行疾病管理。对严重急性呼吸综合征冠状病毒 (SARS-CoV) 的研究强调了草药与抗病毒药物联合使用或单独使用在降低感染严重程度和相关炎症方面的作用。Divya-Swasari-Vati 是一种印度阿育吠陀配方，用于治疗慢性咳嗽和肺部炎症，这是 SARS-CoV-2 感染的首发症状之一。
方法：在这项研究中，我们在斑马鱼的鱼鳔中使用了 A549 细胞异种移植物，并通过给鱼注射重组刺突蛋白来模拟 SARS-CoV-2 感染。不同组给予正常饲料或与地塞米松（作为对照药物）或 Divya-Swasari-Vati 混合饲料。研究了行为发热的变化、鱼鳔中促炎细胞的浸润、肾脏中坏死细胞的退化或存在以及促炎细胞因子的基因表达，以确定患病表型的拯救。
结果：刺突蛋白的挑战导致鳔细胞学发生变化，浸润促炎细胞、皮肤出血和行为发热增加。这也伴随着疾病控制鱼的死亡率增加。Divya-Swasari-Vati 治疗逆转了大部分疾病症状，包括对肾小球细胞的损害，以及完全逆转行为发热。用作比较器的地塞米松只能部分挽救行为发热表型。Divya-Swasari-Vati 还在体内和体外条件下以剂量依赖性方式抑制促炎细胞因子 IL-6 和 TNF-α 的水平。
结论：研究表明，注射 SARS-CoV-2 重组刺突蛋白的 A549 异种移植斑马鱼是该疾病的有效模型；Divya-Swasari-Vati 药物治疗挽救了大部分由病毒刺突蛋白引起的炎症损伤，同时提高了实验鱼的存活率。

关键词：斑马鱼，A549 异种移植，SARS-CoV-2 感染模型，草药，阿育吠陀，Divya-Swasari-Vati，行为热，细胞因子谱