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) 10.1080/0889311X.2024.2309494.

Text Berta_Helicase_review_final_V2.pdf - Accepted Version Access restricted to UCL open access staff until 27 February 2025. Download (1MB)

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.

Download activity - last month

Export as CSVJSONXML

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item