Structure of replicating SARS-CoV-2 polymerase

Hauke S. Hillen, Goran Kokic, Lucas Farnung, Christian Dienemann, Dimitry Tegunov and Patrick Cramer ()
Additional contact information
Hauke S. Hillen: Max Planck Institute for Biophysical Chemistry
Goran Kokic: Max Planck Institute for Biophysical Chemistry
Lucas Farnung: Max Planck Institute for Biophysical Chemistry
Christian Dienemann: Max Planck Institute for Biophysical Chemistry
Dimitry Tegunov: Max Planck Institute for Biophysical Chemistry
Patrick Cramer: Max Planck Institute for Biophysical Chemistry

Nature, 2020, vol. 584, issue 7819, 154-156

Abstract: Abstract The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes1–3. Here we present a cryo-electron microscopy structure of the SARS-CoV-2 RdRp in an active form that mimics the replicating enzyme. The structure comprises the viral proteins non-structural protein 12 (nsp12), nsp8 and nsp7, and more than two turns of RNA template–product duplex. The active-site cleft of nsp12 binds to the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged ‘sliding poles’. These sliding poles can account for the known processivity of RdRp that is required for replicating the long genome of coronaviruses3. Our results enable a detailed analysis of the inhibitory mechanisms that underlie the antiviral activity of substances such as remdesivir, a drug for the treatment of coronavirus disease 2019 (COVID-19)4.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2368-8 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:584:y:2020:i:7819:d:10.1038_s41586-020-2368-8

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2368-8

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().