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Updated: Dec 19, 2025
Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
Published on: December 23, 2020
Structural Basis of RNA Cap Modification by SARS-CoV-2 Coronavirus
Thiruselvam Viswanathan1,2, Shailee Arya1,2, Siu-Hong Chan3
1Greehey Children's Cancer Research Institute, University of Texas Health San Antonio, 8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
Abstract:
The novel severe acute respiratory syndrome coronoavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused over 2 million infections worldwide in four months. In SARS coronaviruses, the non-structural protein 16 (nsp16) methylates the 5'-end of virally encoded mRNAs to mimic cellular mRNAs, thus protecting the virus from host innate immune restriction. We report here the high-resolution structure of a ternary complex of full-length nsp16 and nsp10 of SARS-CoV-2 in the presence of cognate RNA substrate and a methyl donor, S-adenosyl methionine. The nsp16/nsp10 heterodimer was captured in the act of 2'-O methylation of the ribose sugar of the first nucleotide of SARS-CoV-2 mRNA. We reveal large conformational changes associated with substrate binding as the enzyme transitions from a binary to a ternary state. This structure provides new mechanistic insights into the 2'-O methylation of the viral mRNA cap. We also discovered a distantly located ligand-binding site unique to SARS-CoV-2 that may serve as an alternative target site for antiviral development.
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