6YZ1

The crystal structure of SARS-CoV-2 nsp10-nsp16 methyltransferase complex with Sinefungin

Summary for 6YZ1

• Entry DOI: 10.2210/pdb6yz1/pdb
• Descriptor: nsp16, nsp10, SINEFUNGIN, ... (6 entities in total)
• Functional Keywords: sars-cov-2, viral replication, coronavirus, methyltransferase, sinefungin, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 2
• Total formula weight: 47319.96

Authors

Krafcikova, P.,Silhan, J.,Nencka, R.,Boura, E. (deposition date: 2020-05-06, release date: 2020-05-13, Last modification date: 2024-01-24)

Primary citation

Krafcikova, P.,Silhan, J.,Nencka, R.,Boura, E.
Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin.
Nat Commun, 11:3717-3717, 2020

PubMed Abstract: Severe 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.

PubMed: 32709887
DOI: 10.1038/s41467-020-17495-9

Experimental method

X-RAY DIFFRACTION (2.4 Å)