Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	An adenosine analog shows high antiviral potency against coronavirus and arenavirus mainly through an unusual base pairing mode.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 10750, Year 2024
Publish date	Dec 30, 2024
Authors	Xiaoying Jia / Xuping Jing / Ming Li / Minli Gao / Yao Zhong / Entao Li / Yang Liu / Rui Li / Guoqiang Yao / Qiaojie Liu / Minmin Zhou / Yuxia Hou / Linfeng An / Yibao Hong / Shanshan Li / Jiancun Zhang / Wei Wang / Kaiming Zhang / Peng Gong / Sandra Chiu /
PubMed Abstract	By targeting the essential viral RNA-dependent RNA polymerase (RdRP), nucleoside analogs (NAs) have exhibited great potential in antiviral therapy for RNA virus-related diseases. However, most ribose- ...By targeting the essential viral RNA-dependent RNA polymerase (RdRP), nucleoside analogs (NAs) have exhibited great potential in antiviral therapy for RNA virus-related diseases. However, most ribose-modified NAs do not present broad-spectrum features, likely due to differences in ribose-RdRP interactions across virus families. Here, we show that HNC-1664, an adenosine analog with modifications both in ribose and base, has broad-spectrum antiviral activity against positive-strand coronaviruses and negative-strand arenaviruses. Importantly, treatment with HNC-1664 demonstrate anti-SARS-CoV-2 efficacy in infected K18-human ACE2 mice, with reduced viral titer and mortality, as well as improved lung injury. Enzymology data demonstrate that HNC-1664 inhibits RNA synthesis mainly at the pre-catalysis stage. The cryo-EM structures of HNC-1664-bound RdRP-RNA complexes from both SARS-CoV-2 and LASV reveal an unusual base pairing mode of HNC-1664 in part due to its base modification, thus revealing its great potency in binding but not catalysis. Under certain circumstances, 1664-TP can be slowly incorporated by RdRP through regular Watson-Crick base pairing, as evidenced by enzymology data and an HNC-1664-incorporated crystal structure of the RdRP-RNA complex. Overall, HNC-1664 achieves broad-spectrum characteristics by favoring an alternative base pairing strategy to non-catalytically block RNA synthesis, providing a novel concept for the rational development of NA drugs.
External links	Nat Commun / PubMed:39737930 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	3 - 3.29 Å
Structure data	38422 8xko EMDB-38422, PDB-8xko: CryoEM structure of compound HNC-1664 bound with RdRP-RNA complex of SARS-CoV-2 Method: EM (single particle) / Resolution: 3.29 Å 38557 8xpo EMDB-38557, PDB-8xpo: Cryo-EM structure of Lassa virus RdRP elongation complex with the NTP form of compound HNC-1664 bound in the active site Method: EM (single particle) / Resolution: 3.02 Å PDB-8xpp: Crystal structure of the enterovirus 71 RdRP elongation complex with the nucleoside monophosphate form of compound HNC-1664 at product position -1 (post-translocation state) Method: X-RAY DIFFRACTION / Resolution: 3 Å
Chemicals	PDB-1lvz: METARHODOPSIN II BOUND STRUCTURE OF C-TERMINAL PEPTIDE OF ALPHA-SUBUNIT OF TRANSDUCIN ChemComp-MG: Unknown entry ChemComp-ZN: Unknown entry
Source	severe acute respiratory syndrome coronavirus severe acute respiratory syndrome coronavirus 2 synthetic construct (others) lassa virus josiah enterovirus a71
Keywords	VIRAL PROTEIN/RNA / RNA dependent RNA polymerase / SARS-CoV-2 / nucleoside analog / VIRAL PROTEIN / VIRAL PROTEIN-RNA complex / REPLICATION / Lassa virus / RNA-dependent RNA polymerase / elongation complex / enterovirus 71