Effects of high polyphenol doses on the replication of COVID-19 in vitro

SARS-CoV-2的爆发导致了前所未有的全球卫生危机。这种传染性病毒的致死率在总感染人群中接近2%，在老年人中超过15%。到目前为止，还没有药物或疫苗被批准用于治疗这种病毒性疾病。这种RNA病毒与SARS-CoV-1相关，SARS-CoV-1是2002-03年在中国出现的一种相关病毒，但具有引起特定病态症状的独特特征。在实际大流行的背景下，迫切需要重新审视已经开发的合成药物和传统药典中的天然分子，这些药物可能对病毒起作用。将分子重新分类为新的抗病毒用途可以提供快速开发和推荐药物的方法，因为其剂量，副作用，配方和毒性已经知道。在天然药用植物的药典中，类黄酮似乎有希望对抗SARS-CoV-2。事实上，它们显示出对许多病毒的抗病毒活性，如流感，寨卡病毒，埃博拉病毒，肝炎，艾滋病毒和许多其他病毒。表没食子儿茶素没食子酸酯，槲皮素，橙皮苷，所有黄酮类化合物，是进一步活性测试的候选分子，因为它们在重要的病毒蛋白结合位点上具有高对接能力。值得注意的是，前三种分子分别在绿色茶、洋葱和柑橘中浓度很高。可以使用具有相对简单的协议适配的可用技术来有效地提取它们。最有趣的是，这些产品的毒理学已经得到了充分的研究，加拿大卫生部已经有了描述其公认的传统用途、毒性和副作用的专著。我们假设，黄酮类化合物有抑制作用，防止复制SARS-CoV-2在Vero细胞，它是可能的，以开发有效的提取方案，在体外筛选阶段确定的生物活性分子。 我们将特别评估7种多酚（EGCG、槲皮素、异槲皮素、橙皮苷、儿茶素、原花青素、儿茶素、阿魏酸）对SARS-CoV-2体外复制的影响，并开发从不同来源的原料产品中提取这些分子的方案。

The SARS-CoV-2 outbreak in causing an unprecedented global sanitary crisis. The contagious virus has a lethal rate of close to 2% death in the overall affected population and more than 15 % in elderly people. To date, there are no medications or vaccines approved for the treatment of this viral disease. This RNA virus is associated to SARS-CoV-1, a related virus which emerged in 2002-03 in China, but has distinct features provoking specific morbid symptoms. In the context of the actual pandemic, it is urgent to revisit the arsenal of already developed synthetic drugs and natural molecules from the traditional pharmacopeia with potential action against the virus. The reclassification of a molecule to a new anti-viral use can provide a rapid approach to develop and recommend a drug since its dosage, side effects, formulation and toxicity are already known. Among the pharmacopeia of natural medicinal plants, flavonoids appear promising to fight SARS-CoV-2. Indeed, they display antiviral activity against a number of viruses such as influenza, Zika, Ebola, hepatitis, HIV and many others. Epigallocatechin gallate, quercetin, hesperidin, all flavonoids, are candidate molecules for further activity testing owing to their high-docking capacity on important virus protein binding sites. Noteworthy is the fact that the first three molecules are found in high concentrations in green tea, onions, and citrus respectively. They can be extracted efficiently using available technologies with relatively simple protocol adaptation. Most interestingly, the toxicology of these products has been amply studied and Health Canada already has monographies describing their accepted traditional use, toxicity and side effects. We hypothesize that flavonoids have an inhibitory action preventing the replication of SARS-CoV-2 in Vero cells and that it is possible to develop efficient extraction protocols for the bioactive molecules identified during the in vitro screening phases. We will in particular evaluate, 7 polyphenols (EGCG, quercetin, isoquercetin, hesperidin, catechin, proanthocyanidins, catechins, ferulic acid) on replication of SARS-CoV-2 in vitro and develop protocols for the extraction of these molecules from different sources of raw product.