High-resolution structures of the SARS-CoV-2 2'-<i>O</i>-methyltransferase reveal strategies for structure-based inhibitor design.

ABSTRACT: There are currently no antiviral therapies specific for SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an x-ray crystallographic study of the SARS-CoV-2 nsp16-nsp10 2'-O-methyltransferase complex, which methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. We determined the structures for nsp16-nsp10 heterodimers bound to the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH), or the SAH analog sinefungin (SFG). We also solved structures for nsp16-nsp10 in complex with the methylated Cap-0 analog m⁷GpppA and either SAM or SAH. Comparative analyses between these structures and published st

SUBMITTER: Rosas-Lemus M 

PROVIDER: S-EPMC8028745 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature