Advanced Photon Source: How SARS-CoV-2 RNA Evades Host Immune Responses (Gupta Lab)

As we all know too well, the virus SARS-CoV-2 causes severe respiratory illness COVID-19. In parallel with the critical search for a cure, scientists are working diligently to develop effective treatments that can help lower the morbidity of this deadly virus. To develop these therapeutics, we must understand how the virus is able to invade a host’s cells and dodge detection. A recent Nature Communications report based on research carried out at the U.S. Department of Energy’s Advanced Photon Source (APS) reveals key details about how SARS-CoV-2 modifies its messenger RNA and evades immune responses in its host. Using high-resolution x-ray crystallography, the researchers determined a high-resolution structure of the ternary SARS-CoV-2 RNA cap/nsp16/nsp10 complex and the conformational changes that catalytic nsp16 undergoes during RNA cap-binding. The researchers also discovered a distantly located ligand-binding site that allows nsp16 to bind small molecules outside the catalytic pocket. These findings improve our understanding of mRNA capping in coronaviruses and provide a strategy by which scientists could develop small-molecule drugs that will fight and treat the diseases caused by coronaviruses like SARS-CoV-2.

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