9I1S | pdb_00009i1s

Crystal structure of the SARS-CoV-2 helicase NSP13 in complex with myricetin

PDB DOI: https://doi.org/10.2210/pdb9I1S/pdb

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

Deposited: 2025-01-16 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: 2.09 ?
R-Value Free:
0.241 (Depositor), 0.240 (DCC)
R-Value Work:
0.215 (Depositor), 0.214 (DCC)
R-Value Observed:
0.216 (Depositor)

Starting Model: experimental
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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?? 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, G?ttingen Center of Molecular Biosciences (GZMB), University of G?ttingen, Justus-von-Liebig-Weg 11, 37077 G?ttingen, Germany.

Macromolecule Content

Total Structure Weight: 135.81 kDa
Atom Count: 9,222
Modeled Residue Count: 1,156
Deposited Residue Count: 1,206
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Helicase nsp13	A, B	603	Severe acute respiratory syndrome coronavirus 2	Mutation(s): 0 Gene Names: rep, 1a-1b EC: 3.6.4.12 (PDB Primary Data), 3.6.4.13 (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 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MYC (Subject of Investigation/LOI) Query on MYC Download Ideal Coordinates CCD File SDF format, chain O [auth B] MOL2 format, chain O [auth B] mmCIF format, chain O [auth B]	O [auth B]	3,5,7-TRIHYDROXY-2-(3,4,5-TRIHYDROXYPHENYL)-4H-CHROMEN-4-ONE C₁₅ H₁₀ O₈ IKMDFBPHZNJCSN-UHFFFAOYSA-N		Interactions Focus chain O [auth B] Interactions & Density Focus chain O [auth B]
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 C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain K [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain K [auth B] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B] mmCIF format, chain K [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]