New research: Identifying potential targets for drugs that could work against all coronaviruses

Drugs often bind inside “pockets” on proteins that hold the drug snugly, causing it to interfere with the protein’s function. Scientists can identify potential drug-binding pockets from the 3D structures of viral proteins.

The possible emergence of vaccine-resistant SARS-CoV-2 variants, as well as novel coronaviruses, makes it important to find treatments that work against all coronaviruses.

Now, researchers have analysed viral proteins across 27 coronavirus species and thousands of samples from Covid-19 patients, identifying highly conserved sequences that could make the best drug targets. They have reported their findings in the American Chemical Society’s Journal of Proteome Research.

Drugs often bind inside “pockets” on proteins that hold the drug snugly, causing it to interfere with the protein’s function. Scientists can identify potential drug-binding pockets from the 3D structures of viral proteins. Over time, however, viruses can mutate their protein pockets so that drugs no longer fit.

But some drug-binding pockets are so essential to the protein’s function that they can’t be mutated, and these sequences are generally conserved over time in the same virus, and in related viruses.

In the study, researcher Matthieu Schapira and colleagues wanted to find the most highly conserved drug-binding pockets in viral proteins from Covid-19 patient samples and from other coronaviruses, revealing the most promising targets for pan-coronavirus drugs, the American Chemical Society said in a press release on the research.

The team used a computer algorithm to identify drug-binding pockets in the 3D structures of 15 SARS-CoV-2 proteins. The researchers then found corresponding proteins in 27 coronavirus species and compared their sequences in the drug-binding pockets.

The two most conserved “druggable” sites involved proteins (called nsp13 and nsp12 respectively) that are involved in viral RNA replication and transcription.

The researchers said novel antiviral drugs targeting the catalytic site of the protein nsp12 are currently in phase II and III clinical trials for Covid-19, and that the RNA binding site of nsp13 is a previously underexplored target that should be a high priority for drug development.

Source: American Chemical Society

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