Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin
Copyright policy )Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin
AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. 2′-O-RNA methyltransferase (MTase) is one of the enzymes of this virus that is a potential target for antiviral therapy as it is crucial for RNA cap formation; an essential process for viral RNA stability. This MTase function is associated with the nsp16 protein, which requires a cofactor, nsp10, for its proper activity. Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Our structural comparisons reveal low conservation of the MTase catalytic site between Zika and SARS-CoV-2 viruses, but high conservation of the MTase active site between SARS-CoV-2 and SARS-CoV viruses; these data suggest that the preparation of MTase inhibitors targeting several coronaviruses - but not flaviviruses - should be feasible. Together, our data add to important information for structure-based drug discovery.
- Academy of Sciences Library Czech Republic
Models, Molecular, RNA Caps, crystal structure, Adenosine, Science, RNA Stability, Pneumonia, Viral, coronavirus, General Physics and Astronomy, virus, Viral Nonstructural Proteins, Crystallography, X-Ray, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Catalytic Domain, Humans, Viral Regulatory and Accessory Proteins, Enzyme Inhibitors, Pandemics, SARS-CoV-2, Q, COVID-19, General Chemistry, Methyltransferases, Models, Chemical, RNA, Viral, methylation, Coronavirus Infections
Models, Molecular, RNA Caps, crystal structure, Adenosine, Science, RNA Stability, Pneumonia, Viral, coronavirus, General Physics and Astronomy, virus, Viral Nonstructural Proteins, Crystallography, X-Ray, General Biochemistry, Genetics and Molecular Biology, Article, Betacoronavirus, Catalytic Domain, Humans, Viral Regulatory and Accessory Proteins, Enzyme Inhibitors, Pandemics, SARS-CoV-2, Q, COVID-19, General Chemistry, Methyltransferases, Models, Chemical, RNA, Viral, methylation, Coronavirus Infections
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