eprintid: 10190181
rev_number: 9
eprint_status: archive
userid: 699
dir: disk0/10/19/01/81
datestamp: 2024-04-04 18:00:03
lastmod: 2025-02-27 11:42:13
status_changed: 2024-04-04 18:00:03
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Horrell, Sam
creators_name: Martino, Sam
creators_name: Kirsten, Ferdinand
creators_name: Berta, Denes
creators_name: Santoni, Gianluca
creators_name: Thorn, Andrea
title: What a twist: structural biology of the SARS-CoV-2 helicase nsp13
ispublished: pub
divisions: UCL
divisions: B04
divisions: C06
divisions: F60
keywords: SARS-CoV-2; COVID-19;helicase; structural biology;structure based drug design
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: SARS-CoV-2 nsp13 is a multifunctional helicase from helicase superfamily 1B. It unwinds the viral RNA genome for replication and is thought to play a role in 5’ mRNA capping to produce mature mRNA using its triphosphatase activity. The sequence and structure are highly conserved in nidovirales and the protein is essential to the viral infection cycle, acting as a standalone enzyme and in conjunction with other SARS-CoV-2 proteins, making SARS-CoV-2 helicase a promising target for structure-based drug design. By inhibiting helicase activity, phosphatase activity, or its interaction with the RNA-dependent RNA polymerase we could interrupt viral replication. A total of 72 structures of SARS-CoV-2 nsp13 have been published in the protein databank (PDB) to date, 56 monomers and 16 as part of a complex. The structure of nsp13 is made up of five conserved folds, from N- to C-terminus, a zinc-binding domain, stalk domain, beta barrel domain 1B, RecA-like subdomain 1A, and RecA-like subdomain 1B. This review summarizes the current structural and functional knowledge surrounding SARS-CoV-2 nsp13 and related helicases, as well as the structure-based drug design efforts to date, and other complementary knowledge to provide downstream users of SARS-CoV-2 structures with a solid foundation to better inform their work.
date: 2024-02-26
date_type: published
publisher: Taylor & Francis
official_url: https://doi.org/10.1080/0889311X.2024.2309494
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2254992
doi: 10.1080/0889311X.2024.2309494
lyricists_name: Berta, Denes
lyricists_id: DGBER83
actors_name: Zahnhausen-Stuber, Petra
actors_id: PMZAH20
actors_role: owner
funding_acknowledgements: [Corona Virus Structural Task Force]
full_text_status: public
publication: Crystallography Reviews
volume: 29
number: 4
pagerange: 202-227
pages: 26
issn: 0889-311X
citation:        Horrell, Sam;    Martino, Sam;    Kirsten, Ferdinand;    Berta, Denes;    Santoni, Gianluca;    Thorn, Andrea;      (2024)    What a twist: structural biology of the SARS-CoV-2 helicase nsp13.                   Crystallography Reviews , 29  (4)   pp. 202-227.    10.1080/0889311X.2024.2309494 <https://doi.org/10.1080/0889311X.2024.2309494>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10190181/1/Berta_Helicase_review_final_V2.pdf