SARS-CoV-2 害怕绿色：叶绿素分解代谢物脱镁叶酸 A 是一种有效的抗病毒药物,Pharmaceuticals

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SARS-CoV-2 害怕绿色：叶绿素分解代谢物脱镁叶酸 A 是一种有效的抗病毒药物
Pharmaceuticals ( IF 4.286 ) Pub Date : 2021-10-15 , DOI: 10.3390/ph14101048
Guillermo H Jimenez-Aleman ₁ , Victoria Castro ₂ , Addis Londaitsbehere ₁ , Marta Gutierrez-Rodríguez ₃ , Urtzi Garaigorta ₂ , Roberto Solano ₁ , Pablo Gastaminza ₂

Affiliation

SARS-CoV-2 大流行正在全球范围内造成毁灭性后果。尽管疫苗接种进展顺利，但针对新出现的变异的有效性是不可预测的。该病毒对治疗表现出显着的抵抗力，并且没有任何药物被证明对 COVID-19 完全有效。因此，尽管国际上做出了努力，但仍然迫切需要针对 SARS-CoV-2 的新型有效且安全的抗病毒药物。在这里，我们利用苔藓植物Marchantia polymorpha开发了植物代谢的巨大潜力L. 并根据生物活性引导的分馏和质谱方法确定了一种有效的 SARS-CoV-2 抗病毒药物。我们发现叶绿素衍生物 Pheophorbide a (PheoA) 是一种类似于动物原卟啉 IX 的卟啉化合物，对 SARS-CoV-2 具有非凡的抗病毒活性，可防止培养的猴子和人类细胞感染，而且没有明显的细胞毒性。我们还表明 PheoA 靶向病毒颗粒，以剂量和时间依赖性方式干扰其传染性。除了 SARS-CoV-2，PheoA 还显示出对包膜 RNA 病毒病原体（如 HCV、西尼罗河和其他冠状病毒）的广谱抗病毒活性。我们的结果表明 PheoA 显示出显着的效力和令人满意的治疗指数，

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SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral

SARS-CoV-2 pandemic is having devastating consequences worldwide. Although vaccination advances at good pace, effectiveness against emerging variants is unpredictable. The virus has displayed a remarkable resistance to treatments and no drugs have been proved fully effective against COVID-19. Thus, despite the international efforts, there is still an urgent need for new potent and safe antivirals against SARS-CoV-2. Here, we exploited the enormous potential of plant metabolism using the bryophyte Marchantia polymorpha L. and identified a potent SARS-CoV-2 antiviral, following a bioactivity-guided fractionation and mass-spectrometry approach. We found that the chlorophyll derivative Pheophorbide a (PheoA), a porphyrin compound similar to animal Protoporphyrin IX, has an extraordinary antiviral activity against SARS-CoV-2, preventing infection of cultured monkey and human cells, without noticeable cytotoxicity. We also show that PheoA targets the viral particle, interfering with its infectivity in a dose- and time-dependent manner. Besides SARS-CoV-2, PheoA also displayed a broad-spectrum antiviral activity against enveloped RNA viral pathogens such as HCV, West Nile, and other coronaviruses. Our results indicate that PheoA displays a remarkable potency and a satisfactory therapeutic index, which together with its previous use in photoactivable cancer therapy in humans, suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.

更新日期：2021-10-15

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