Finding the molecular structures that Sars-CoV-2 variants share with other coronavirus species is the first step towards the development of a drug potentially capable of fighting not only current infections, but also those of the coronaviruses of the future, and their future variants. This was the scientific challenge undertaken by a group of researchers from the University of Toronto.
The approach starts from a very practical consideration: proteins (including those of coronaviruses) have a molecular structure that has several “pockets”, or recesses that allow a healing molecule to bind to the protein, sticking like a key in the lock. These “pockets” are therefore essential for a drug to act on that protein.
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Canadian researchers, coordinated by the pharmacologist Matthieu Schapira, studied the viral protein structures of 27 coronavirus species – and thousands of Sars-CoV-2 samples isolated from infected patients – looking for the proteins shared by as many coronaviruses as possible and identifying, on the protein structure, the ” pockets “possible targets of a drug. Result: Two proteins were found, involved in viral RNA replication, shared by all 27 coronavirus species. These are the proteins “nsp12” and “nsp13”.
Why are these two important proteins, Professor Schapira?
The fact that they are present, and preserved almost identical, in all the coronavirus species we have analyzed – including also the coronaviruses of the 2003 SARS and 2012 MERS – indicates that they are essential. Viruses mutate, as we know. But if they maintain the same precise protein structures it means that these are very important. If they weren’t, they could have been absent, or mutated, in some of the samples studied – as is the case with many other less crucial proteins.
Let us better understand how this approach could lead to a universal coronavirus drug.
I state that the global vaccination campaign is still the best approach to stop the Covid-19 pandemic. However, today the target of vaccines is a protein, the Spike protein, which is not one of those that are most kept identical in the various coronaviruses. On the other hand, the two proteins we have considered, and in particular nsp13, do not change. A drug that attacks these proteins, to prevent the virus from replicating after infection, could therefore work for all coronaviruses.
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Here, the key word is “could” …
If the virus does not mutate in those proteins, there must be a good evolutionary reason that prevents the mutation. Or rather: that it prevents that, when those proteins mutate by chance, the mutated virus from replicating. The reasoning is that if there has been a good reason to prevent those mutations in the past, there should also be for future evolutions of Sars-CoV-2 (and other coronaviruses).
Have you verified that the various coronaviruses, when these two proteins are inactivated, are no longer able to replicate?
This has been seen in vitro, but not yet in patients. Especially for the nsp13 protein, there is still a lot to understand: so far this protein has been somewhat neglected in Covid research. Our approach has yet to be clinically tested.
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