Heme oxygenase-1 inducer hemin does not inhibit SARS-CoV-2 virus infection.
Heme oxygenase-1 inducer hemin does not inhibit SARS-CoV-2 virus infection.
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DOI：
10.1016/j.biopha.2021.111384
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Fontanellas A
中科院分区：
文献类型：
--
作者：
Maestro S;Córdoba KM;Olague C;Argemi J;Ávila MA;González-Aseguinolaza G;Smerdou C;Fontanellas A
不同作用机制的抗病毒药物可诱导对SARS-CoV-2感染的协同作用。一些报道表明血红素加氧酶-1 （HO-1）酶具有治疗病毒感染的潜力。鉴于血凝素是HO-1基因的天然诱导剂，本研究的目的是建立一种体外实验来分析血凝素对SARS-CoV-2感染的抗病毒效力。在Vero-E6和Calu-3上皮细胞系中进行了SARS-CoV-2传染性试验。利用N基因特异性寡核苷酸，采用RT-qPCR方法定量检测血红素和对照氯喹对SARS-CoV-2病毒感染的抗病毒作用。氯喹诱导肾上皮细胞Vero-E6中病毒基因组拷贝数的显著减少，但在肺癌细胞Calu-3中没有。Hemin对HO-1基因表达的诱导作用在Vero-E6猕猴源细胞中强于在人Calu-3细胞系中。然而，在Vero-E6感染后48小时和Calu-3谱系感染后72小时，通过病毒基因组量化测量，hemin治疗没有改变SARS-CoV-2的复制。综上所述，尽管暴露于血红素诱导了HO-1的强烈上调，但这种作用不能抑制或延缓两种易感上皮细胞系的SARS-CoV-2感染的进展。
Antiviral agents with different mechanisms of action could induce synergistic effects against SARS-CoV-2 infection. Some reports suggest the therapeutic potential of the heme oxygenase-1 (HO-1) enzyme against virus infection. Given that hemin is a natural inducer of the HO-1 gene, the aim of this study was to develop an in vitro assay to analyze the antiviral potency of hemin against SARS-CoV-2 infection. A SARS-CoV-2 infectivity assay was conducted in Vero-E6 and Calu-3 epithelial cell lines. The antiviral effect of hemin, and chloroquine as a control, against SARS-CoV-2 virus infection was quantified by RT-qPCR using specific oligonucleotides for the N gene. Chloroquine induced a marked reduction of viral genome copies in kidney epithelial Vero-E6 cells but not in lung cancer Calu-3 cells. Hemin administration to the culture medium induced a high induction in the expression of the HO-1 gene that was stronger in Vero-E6 macaque-derived cells than in the human Calu-3 cell line. However, hemin treatment did not modify SARS-CoV-2 replication, as measured by viral genome quantification 48 h post-infection for Vero-E6 and 72 h post-infection for the Calu-3 lineages. In conclusion, although exposure to hemin induced strong HO-1 up-regulation, this effect was unable to inhibit or delay the progression of SARS-CoV-2 infection in two epithelial cell lines susceptible to infection.
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