The result comes from a study by the Federico II University of Naples and that of Perugia
The researchers identified endogenous molecules that could prevent the virus from entering human cells. Endogenous molecules are steroid in nature and some of them are bile acids, substances produced in the liver and intestines by cholesterol metabolism.
“It is a substance already present in the body – explains Angela Zampella, director of the Department of Pharmacy of the University of Naples Federico II – that blocks the entry of the virus into the cells”.
It is completely natural also present in foods such as licorice and olive oil and “act with the same mechanism”.
A discovery that paves the way for a different prevention also because, as Zampella says, “it works when the virus load is not very high”.
The pre-print study on the BioRxiv website combined computational approaches from Bruno Catalanotti’s group, synthetic chemistry, Angela Zampella, and molecular biology from Adriana Carino, led by professor Stefano Fiorucci, and also involved the team of microbiology and infectious diseases of the University of Perugia.
The study was conducted through a first in silico (computational) screening of libraries of natural substances and drugs approved for clinical use by the Food and Drug Administation (FDA, USA) and allowed the identification of functional “pockets” in the structure of the receptor binding domain (Rbd) of the Spike protein of the Sars-Cov2 virus. The further characterization of these structures led to the discovery of the existence of endogenous substances capable of interfering in the binding of the spike Rdb with the Ace2 receptor (Angiotensin Converting Enzyme 2).
The study, Zampella says, is the first step in drawing up a therapeutic protocol that will be proposed to Aifa’s attention.
Primary bile acids, i.e. those generated in the liver, bind, although with low efficiency, Spike’s Rdb, while bile acids currently used in therapy (ursodessocolic acid) and their metabolites inhibit the bond between Spike’s Rbd and Ace2 of approximately 50%. Semi-synthetic bile acids also possess this ability.
Like endogenous bile acids, natural substances, such as some triterpenoids (betulinic acid, oleanolic acid and glycyrrhizic acid), are able to bind Spike’s Rbd and are moderately effective in reducing the bond with Ace2.
Finally, drugs and their steroid-based metabolites (e.g. potassium carnenoate) interfere with the bond between Spike and Ace2.
The work was supported by a research grant from Bar Pharmaceuticals SrL to the two universities and the results were the subject of a patent application.
“The different studies – the researchers highlight – have shown that the mutation of the Spars protein of Sars-Cov2 confers affinity for the virus for a complementary protein sequence localized on the carboxypeptidase region of the human Ace2 receptor, which metabolizes angiotensin II to generate angiotensin 1- 7 “.
A link necessary for the link “another enzyme, Tmprss2, to separate the S1 sequence from Spike’s S2.” In short, the Sars-Cov2 virus ‘pirated’ a human receptor “. As a result, as researchers conclude, our body possesses also defensive mechanisms capable of reducing the ability of the virus to bind its target receptor “.