Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, 10032, USA.
J Ethnopharmacol. 2021 Jun 28;274:114016. doi: 10.1016/j.jep.2021.114016. Epub 2021 Mar 12.
Artemisia annua L. has been used for millennia in Southeast Asia to treat "fever". Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria.
SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2.
Using Vero E6 and Calu-3 cells, we measured anti SARS-CoV-2 activity against fully infectious virus of dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as the concentrations that inhibited viral replication by 50%; CC50s were also calculated and defined as the concentrations that kill 50% of cells.
Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC values of 0.1-8.7 μM, 0.01-0.14 μg, and 23.4-57.4 μg, respectively. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet its hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC of about 70 μM, and the clinically used artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC = 5.8 μM. Extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude above the antiviral IC values.
A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.
青蒿素在东南亚地区已被使用了数千年，用于治疗“发热”。许多传染性微生物和病毒疾病已被证明对青蒿素有反应，世界各地的社区将该植物用作药用茶，特别是用于治疗疟疾。
全球范围内的 SARS-CoV-2（导致 COVID-19 的病毒）已感染并杀死了数百万人。由于青蒿素具有广谱抗病毒活性，包括阻断 SARS-CoV-1，我们想知道青蒿素是否可以抑制 SARS-CoV-2。
使用 Vero E6 和 Calu-3 细胞，我们测量了来自四个大陆的七种青蒿品种的干叶提取物对完全传染性病毒的抗 SARS-CoV-2 活性。计算了 IC50 并将其定义为抑制病毒复制 50%的浓度；还计算并定义了 CC50 为杀死 50%细胞的浓度。
基于青蒿素、总黄酮或干叶质量的热水叶提取物显示出抗病毒活性，IC 值分别为 0.1-8.7 μM、0.01-0.14 μg 和 23.4-57.4 μg。抗病毒功效与提取物中的青蒿素或总黄酮含量无关。一个干叶样本已经有 12 年的历史了，但它的热水提取物仍然具有活性。英国和南非的变异株 B1.1.7 和 B1.351 也同样受到抑制。虽然所有热水提取物都有效，但提取物中青蒿素和总黄酮的浓度相差近 100 倍。青蒿素本身的估计 IC 值约为 70 μM，临床上使用的青蒿素衍生物青蒿琥酯、蒿甲醚和双氢青蒿素在升高的微摩尔浓度下无效或细胞毒性。相比之下，抗疟药阿莫地喹的 IC = 5.8 μM。提取物对 Vero E6 或 Calu-3 细胞感染由 SARS-CoV-2 刺突蛋白假型化的报告病毒的影响很小。在高于抗病毒 IC 值一个数量级的范围内，没有细胞毒性。
青蒿素提取物抑制 SARS-CoV-2 感染，提取物中的活性成分（或成分组合）可能不是青蒿素，而是阻断病毒进入宿主细胞后感染的某个步骤。进一步的研究将确定体内疗效，以评估青蒿素是否可以提供一种具有成本效益的治疗 SARS-CoV-2 感染的方法。
