The recent article “Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening” published in the International Journal of Biological Macromolecules, in addition to having aroused much interest within the scientific community, produced a sudden and strong media impact on the population.
In fact, the network is full of enthusiastic phrases such as “Caper will save us” and “Capers, red onions and radicchio. Here are the new “pharmacological” ways against Covid that nature offers us” that can easily break through the people’s hearts and brains.
The discovery of the research group of the CNR of Cosenza in collaboration with Spanish institutes is now universally known: a fundamental protein for cell replication, 3CLpro, common in the various strains of coronavirus and structurally very different from human variants, which potentially makes it a broad-spectrum and non-toxic target for humans, has been studied and characterized with specific biophysical techniques that have made it possible to evaluate its stability and behaviour to different stimuli and identify “weak points” that can be a target to counteract the virus activity.
In vitro tests and molecular modeling were conducted, in fact reproducing the activity of 3CLpro in a test tube and studying by computational techniques and the aid of specific software how various substances, definable as potential inhibitors, can actually interact and interfere with the activity and structure of the protein.
Among the 150 molecules tested, quercetin, a polyphenolic substance present in many vegetables that we commonly eat, such as capers, onion and radicchio and known for some time in the world of food supplementation for its various properties, was the winner. A concentration of quercetin equal to 7µM, corresponding to about 2 µg / L, inhibited the action of 3CLpro by half, thus demonstrating sufficient activity to hypothesize a future use of quercetin as a “scaffold” for the development of new drugs for the treatment of COVID-19 and as a starting point for subsequent pre-clinical and clinical tests on laboratory animals and humans.
The study, therefore, represents an interesting and valid theoretical premise which, however, remains limited to computational predictions and tests recreated in the laboratory and does not investigate the possible contribution of quercetin taken with food, nor the actual action in humans and the related effective dosages. In fact, it should be considered that once quercetin is taken it does not remain unchanged but undergoes changes in the intestine and liver. Its absorption in the intestinal tract is highly variable from subject to subject and it is undoubtedly necessary to investigate whether the inhibition dose identified for 3CLpro is actually achievable in plasma. In conclusion, to understand whether quercetin can actually constitute a beginning for the initiation of a therapeutic path, further studies will be required that consider the real complexity of what happens when quercetin is taken by a living organism.