2′-O methylation of RNA cap in SARS-CoV-2 captured by serial crystallography

Mateusz Wilamowski, Darren A. Sherrell, George Minasov, Youngchang Kim, Ludmilla Shuvalova, Alex Lavens, Ryan Chard, Natalia Maltseva, Robert Jedrzejczak, Monica Rosas-Lemus, Nickolaus Saint, Ian T. Foster, Karolina Michalska, Karla J.F. Satchell, Andrzej Joachimiak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has a capping modification at the 5′-untranslated region (UTR) to prevent its degradation by host nucleases. These modifications are performed by the Nsp10/14 and Nsp10/16 heterodimers using S-adenosylmethionine as the methyl donor. Nsp10/16 heterodimer is responsible for the methylation at the ribose 2′-O position of the first nucleotide. To investigate the conformational changes of the complex during 2′-O methyltransferase activity, we used a fixed-target serial synchrotron crystallography method at room temperature. We determined crystal structures of Nsp10/16 with substrates and products that revealed the states before and after methylation, occurring within the crystals during the experiments. Here we report the crystal structure of Nsp10/16 in complex with Cap-1 analog (m7GpppAm2-O). Inhibition of Nsp16 activity may reduce viral proliferation, making this protein an attractive drug target.

Original languageEnglish (US)
Article numbere2100170118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number21
StatePublished - May 25 2021


  • Nsp10/16 | SARS-CoV-2 | mRNA | CAP-1 | serial crystallography

ASJC Scopus subject areas

  • General


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