TY - JOUR
AU - Kloskowski, Patrick
AU - Neumann, Piotr
AU - Kumar, Priya
AU - Berndt, Annette
AU - Dobbelstein, Matthias
AU - Ficner, Ralf
TI - Myricetin-bound crystal structure of the SARS-CoV-2 helicase NSP13 facilitates the discovery of novel natural inhibitors
JO - Acta crystallographica / Section D
VL - 81
IS - 6
SN - 0907-4449
CY - Bognor Regis
PB - Wiley
M1 - PUBDB-2025-02293
SP - 310 - 326
PY - 2025
AB - 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.
LB - PUB:(DE-HGF)16
C6 - pmid:40421686
DO - DOI:10.1107/S2059798325004498
UR - https://bib-pubdb1.desy.de/record/632965
ER -