Opening of a cryptic pocket in the SARS-CoV-2 Nsp16 protein with pan-coronavirus antiviral potential
The Nsp16 protein from the SARS-CoV-2 virus plays an essential role in the virus' ability to evade an immune response. Folding@home simulations have revealed a cryptic pocket (red) that is absent in existing crystal structures of the protein. Opening of the cryptic pocket closes up the SAM-binding pocket (SAM is a molecule needed for nsp16 to function, shown in pink sticks). Since having the SAM-binding pocket open is essential for Nsp16 to function properly, a drug that targets the cryptic pocket and closes up the SAM-binding pocket could turn Nsp16 off. We also found that the Nsp16 proteins from the SARS-CoV-1 and MERS viruses have the same cryptic pocket, while this pocket is absent in human proteins that perform a similar function. Therefore, a drug that targets this cryptic pocket could be useful against many/all coronaviruses with minimal side effects.
This video was made by Neha Vithani and Michael Ward at Washington University in St. Louis.
Read more about this work at: https://www.biorxiv.org/content/10.11...
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