TY - JOUR KW - SARS-CoV-2; COVID-19;helicase; structural biology;structure based drug design IS - 4 SN - 0889-311X ID - discovery10190181 VL - 29 N2 - 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. AV - public EP - 227 Y1 - 2024/02/26/ UR - https://doi.org/10.1080/0889311X.2024.2309494 A1 - Horrell, Sam A1 - Martino, Sam A1 - Kirsten, Ferdinand A1 - Berta, Denes A1 - Santoni, Gianluca A1 - Thorn, Andrea SP - 202 N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. TI - What a twist: structural biology of the SARS-CoV-2 helicase nsp13 PB - Taylor & Francis JF - Crystallography Reviews ER -