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New protein target may help fight COVID-19

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Developing innovative treatments against SARS-CoV-2 remains a public health challenge, as new variants are constantly emerging. Currently, viral surface proteins (such as the spike protein) are favored therapeutic targets. However, SARS-CoV-2 also uses cellular resources to create 16 nonstructural proteins that are essential for its replication after entering the cell. One such protein, Nsp1, has been largely unstudied so far. Although an important infectious agent, Nsp1 lacked obvious surface cavities for immobilizing potential drugs.

The research team used the algorithm to run simulations to reveal a cryptic partially hidden pocket on the surface of Nsp1. After experimentally screening many small molecules that could bind to the Nsp1 cavity, they identified one of his (5-acetylaminoindane or 2E10). This pocket was a viable drug target.

In infected cells, Nsp1 acts as a ‘cork’ that prevents host mRNA expression. Binding of a ligand to the cryptic pocket of Nsp1 can prevent this blockade and restore the ribosome’s ability to initiate mRNA translation. The researchers argue that the methods developed to discover her hidden Nsp1pocket could help reveal unknown cavities on the surface of other proteins.

“These results pave the way for the development of new therapeutics that target the Nsp1 protein, not only against SARS-CoV-2 and its variants, but also against other Nsp1-present coronaviruses.” said UNIGE co-author Dr. Francesco Luigi Gervasio. , said in his statement.

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