9I4V | pdb_00009i4v

Crystal structure of the SARS-CoV-2 helicase NSP13

PDB DOI: https://doi.org/10.2210/pdb9I4V/pdb

Classification: HYDROLASE
Organism(s): Severe acute respiratory syndrome coronavirus 2
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2025-01-27 Released: 2025-06-11
Deposition Author(s): Kloskowski, P., Neumann, P., Ficner, R.
Funding Organization(s): German Research Foundation (DFG)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.33 Å
R-Value Free:
0.254 (Depositor), 0.253 (DCC)
R-Value Work:
0.213 (Depositor), 0.213 (DCC)
R-Value Observed:
0.215 (Depositor)

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.0 of the entry. See complete history.

Literature

Myricetin-bound crystal structure of the SARS-CoV-2 helicase NSP13 facilitates the discovery of novel natural inhibitors.

Kloskowski, P., Neumann, P., Kumar, P., Berndt, A., Dobbelstein, M., Ficner, R.

(2025) Acta Crystallogr D Struct Biol 81: 310-326

PubMed: 40421686 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S2059798325004498
Primary Citation of Related Structures:
9I1S, 9I4V

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.

Organizational Affiliation

Department of Molecular Structural Biology, Institute of Microbiology and Genetics, Göttingen Center of Molecular Biosciences (GZMB), University of Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.

Macromolecule Content

Total Structure Weight: 135.49 kDa
Atom Count: 9,066
Modeled Residue Count: 1,155
Deposited Residue Count: 1,206
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
SARS-CoV-2 helicase NSP13	A, B	603	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 0 Gene Names: rep, 1a-1b EC: 3.4.19.12 (PDB Primary Data), 3.4.22 (PDB Primary Data), 3.4.22.69 (PDB Primary Data), 2.7.7.48 (PDB Primary Data), 3.6.4.12 (PDB Primary Data), 3.6.4.13 (PDB Primary Data), 3.1.13 (PDB Primary Data), 3.1 (PDB Primary Data), 2.1.1 (PDB Primary Data)
UniProt
Find proteins for P0DTD1 (Severe acute respiratory syndrome coronavirus 2) Explore P0DTD1 Go to UniProtKB: P0DTD1
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P0DTD1
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MPO Query on MPO Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain N [auth B] MOL2 format, chain H [auth A] MOL2 format, chain N [auth B] mmCIF format, chain H [auth A] mmCIF format, chain N [auth B]	H [auth A], N [auth B]	3[N-MORPHOLINO]PROPANE SULFONIC ACID C₇ H₁₅ N O₄ S DVLFYONBTKHTER-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain N [auth B] Interactions & Density Focus chain H [auth A] Focus chain N [auth B]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain L [auth B] SDF format, chain M [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B] MOL2 format, chain M [auth B] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain L [auth B] mmCIF format, chain M [auth B]	F [auth A], G [auth A], L [auth B], M [auth B]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain L [auth B] Focus chain M [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain L [auth B] Focus chain M [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain K [auth B] SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain I [auth B] SDF format, chain J [auth B] MOL2 format, chain E [auth A] MOL2 format, chain K [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] mmCIF format, chain E [auth A] mmCIF format, chain K [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B]	C [auth A] D [auth A] E [auth A] I [auth B] J [auth B] C [auth A], D [auth A], E [auth A], I [auth B], J [auth B], K [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain K [auth B]