The study of three scientists from the Italian Institute of Technology, Scuola Superiore Sant’Anna, University of Milan: the first step of what could become a drug, based on the use of an aptamer, has been patented
A new strategy to hinder coronavirus infection and its rapid spread among cells: the result of a joint study between the Italian Institute of Technology, Scuola Superiore Sant’Anna and the University of Milan, published in the journal Pharmacological Research
. Paolo Ciana (professor of Pharmacology at the University of Milan), Vincenzo Lionetti (professor of Anesthesiology at the Scuola Superiore Sant’Anna) and Angelo Reggiani (senior researcher and principal investigator in Pharmacology at the Italian Institute of Technology) wondered if there is the possibility of blocking the advancement of the infection by any variant of Sars-CoV-2, hiding that part of the ACE2 receptor (an amino acid called K353) that the virus uses to enter human cells. The experiments gave an affirmative answer.
New therapeutic approach
Scientists have therefore patented the first piece of what could become a drug, based on the use of a DNA aptamer, or a short oligonucleotide strand, capable of binding specifically to K353, making it inaccessible to the Spike protein of any coronavirus and thus preventing cell infection. For the authors, thanks to this study it will be possible to develop a new precision therapeutic approach to prevent Covid infection in a severe form, without stimulating the immune system or having important side effects. We asked Angelo Reggiani to explain the importance of the discovery.
So how would any new anti-Covid drug behave?
At the basis of our study is the idea of creating a “protective screen” with which to hide the entrance door to the cell from the virus – explains Reggiani -. In this way, not being able to infect the target cell, the virus dies. We have identified two aptamers able to bind effectively to the ACE2 receptor, “hiding” it.
What are aptamers?
They are single-stranded DNA fragments that behave like drugs, but they have a specific task and they do just that. To understand each other, as if they put a mask on the access door of the virus (K353), which is located on the ACE2 protein. Aptamers do not enter the cell nucleus and are unable to interact with our DNA.
How was the study carried out?
We computerized the portion of ACE2 that contains K353 and then ran a screening in vitro on millions of aptamers (or artificially created fragments of DNA), finding precisely two that bind very well to this region of ACE2, hiding its presence from the virus. So we did the study on cell lines, first using a piece of Spike protein and then developing the actual Sars-CoV-2 infection in the cells. The results showed that the starting idea was correct: thanks to the aptamers the virus did not bind to the cells, not finding what we have defined as the “gateway”, that is K353.
What are the next steps?
To proceed with the work and arrive, as we hope, to have a new therapy against Covid, two steps are needed: the first is to find a formulation that allows the drug to get there where it needs to act. Aptamers, once introduced into the blood, are very unstable: it is therefore necessary to prevent them from degrading. The second point is to demonstrate that this eventual therapy is not toxic to humans. We know aptamers are not immunogenic, that is, they do not trigger an immune response, but we cannot predict a priori whether, as a chemical substance, it can cause side effects.
How and when could the drug be taken?
At any time of the infection, but obviously the sooner the therapy is started the better. Presumably the therapy should continue until recovery. The big advantage is that the aptamer is independent of the presence of mutations, so it could work with all variants. In fact, the mutations do not concern the “gateway” into the cell. Theoretically, the drug could be effective against any type of coronavirus that uses the Spike protein to infect human cells via the ACE2 receptor.
Is the quest to get to the therapy you described moving forward?
The costs of the development phase of a new drug are very high and we can only access the research funds of our institutes – concludes Reggiani -. Hope to find a company or a lender who believes in the approach we have developed. We have patented the anti-Covid aptamers precisely in order to be able to license the patent exclusively to a company interested in producing the drug, once the clinical trials on humans are concluded.
December 6, 2021 (change December 6, 2021 | 10:42)
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