9I4V

Crystal structure of the SARS-CoV-2 helicase NSP13

Summary for 9I4V

• Entry DOI: 10.2210/pdb9i4v/pdb
• Related: 9I1S
• Descriptor: SARS-CoV-2 helicase NSP13, ZINC ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: nsp13, helicase, sars-cov-2, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2
• Total number of polymer chains: 2
• Total formula weight: 135488.47

Authors

Kloskowski, P.,Neumann, P.,Ficner, R. (deposition date: 2025-01-27, release date: 2025-06-11)

Primary citation

Kloskowski, P.,Neumann, P.,Kumar, P.,Berndt, A.,Dobbelstein, M.,Ficner, R.
Myricetin-bound crystal structure of the SARS-CoV-2 helicase NSP13 facilitates the discovery of novel natural inhibitors.
Acta Crystallogr D Struct Biol, 81:310-326, 2025

PubMed Abstract: The SARS-CoV-2 helicase NSP13 is a highly conserved and essential component of the viral replication machinery, making it a promising target for antiviral drug development. Here, we present the 2 Å resolution crystal structure of NSP13 bound to the natural flavonoid myricetin, revealing a conserved allosteric binding site. Guided by these structural findings, a virtual screening campaign identified the caffeic acid derivatives rosmarinic acid and chlorogenic acid as potential novel natural inhibitors, which were experimentally validated to inhibit RNA-unwinding activity. This study provides structural insights that could support ongoing drug-discovery efforts targeting NSP13 in SARS-CoV-2 and other coronaviruses with pandemic potential.

PubMed: 40421686
DOI: 10.1107/S2059798325004498

Experimental method

X-RAY DIFFRACTION (2.33 Å)