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